Developing a consensus-based competency framework for hospital pharmacists in the management of advanced therapy medicinal products (ATMPs): a modified delphi study in Macao

Abstract

Background

As advanced therapy medicinal products (ATMPs) increasingly enter clinical practice worldwide, many emerging markets still lack standardized pharmacy practice guidance. Macao represents one such setting where ATMP adoption is growing, yet structured competency expectations for hospital pharmacists remain limited. This study aims to develop and content-validate a competency framework (CF) for hospital pharmacists in the clinical use and management of ATMPs.

Methods

A modified Delphi process incorporating the RAND/UCLA Appropriateness Method was conducted in accordance with the ACcurate COnsensus Reporting Document (ACCORD) guideline. A pharmacist expert panel (n = 15) assessed the preliminary CF through two iterative Delphi rounds using a nine-point Likert scale. Items with the disagreement index (DI) < 1 were considered appropriate for inclusion. Reliability was evaluated with Cronbach’s α and the authority coefficient (Cr).

Results

From the 53 potential competencies derived from a previous literature review, international guidelines, and expert opinions, all items were rated as appropriate by 15 panelists in the first Delphi round. However, revisions were proposed for 33 items based on appropriateness ratings and qualitative feedback. The revised CF was re-evaluated by 14 panelists in the second Delphi round, during which nine items were further refined to finalize the CF. Panelist feedback primarily focused on defining pharmacists’ responsibilities in ATMP management, ensuring quality assurance, clarifying procedures for preparation, dispensing, and transportation, and specifying the roles of pharmacy technicians in Macao hospitals. The finalized CF delineates pharmacists’ core competencies across six domains, covering ATMP governance and compliance, prescription evaluation, handling and storage, preparation processes, issue and transportation, administration and monitoring. Cronbach’s α indicated high internal consistency (0.975–0.979), and the average expert authority coefficients were satisfactory (0.70) in both rounds.

Conclusion

A consensus-based CF specific for pharmacists involved in ATMP management was developed in Macao, and its content validity was supported through a modified Delphi process. This CF provides a structured basis for strengthening pharmacists’ competencies and offers a transferable reference for policy and practice across other emerging healthcare systems.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12909-026-09078-x.

Background

Advanced therapy medicinal products (ATMPs), which are based on genes, cells, or tissues, have been developing rapidly worldwide [1]. According to the latest definition issued by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) in June 2025, ATMPs refer to products regulated under the pharmaceutical pathway, including ex vivo-manufactured cell and gene therapies, as well as other products developed using innovative technologies or methods involving microorganisms, cells, genes, or tissue engineering [2]. In this study, “ATMPs” specifically refers to products under this regulatory category. While these therapies offer new treatment possibilities for diseases with limited or no effective options, their technological and managerial complexities in research, manufacturing, and clinical application impose new requirements for quality assurance, risk management, and multidisciplinary collaboration within healthcare institutions [3, 4].

In this context, the expertise and competencies of multidisciplinary healthcare teams are critical for the safe and effective implementation of innovative therapies in clinical practice [5, 6]. As integral members of these teams, it has been reported that pharmacists play a crucial role in supporting the management and care of patients receiving ATMPs in hospital settings. Their responsibilities encompass the procurement, prescribing, preparation, administration, and monitoring of ATMPs, as well as the development of related human resources. Effective pharmacist interventions across these domains are expected to enhance pharmaceutical practice, strengthen multidisciplinary collaboration, and ultimately improve patient outcomes [7].

Given the expanding and increasingly complex responsibilities of pharmacists in the field of ATMPs, a clearly defined set of core competencies is essential to ensure safe, effective, and evidence-based practice [7, 8]. Since the concept of “competency” was introduced in the 1960s, it has been widely applied in healthcare professional development [9, 10]. The terms “competence”, “competency”, and “competencies” are often used interchangeably. Yet, they represent distinct conceptual levels [11]. Competence refers to the overall ability or capacity to perform a specific role effectively. It is an outcome-oriented construct that focuses on what a person can accomplish. In contrast, competency denotes an underlying characteristic, such as knowledge, skills, motives, or personal attributes that enable effective performance. The plural form competencies usually refer to a defined set of these characteristics required for effective performance within a specific context. Accordingly, a competency framework (CF) provides an organized structure that maps these competencies across roles or proficiency levels, guiding assessment, development, and alignment of workforce capability [12]. A prominent example is the Global Competency Framework (GbCF) developed by the International Pharmaceutical Federation (FIP) in 2012, which also informed the inclusion of competency development within the Pharmaceutical Workforce Development Goals [13, 14].

The development of pharmacist CFs provides a consistent basis for professional education, licensure, and continuing professional development. Existing CFs for pharmacists and other healthcare professionals (HCPs) have been adapted or localized across jurisdictions to reflect variations in healthcare needs, scopes of practice, regulatory requirements, and educational structures [9, 15, 16]. For instance, the clinical pharmacist competency framework proposed by the American College of Clinical Pharmacy (ACCP) emphasizes clinical decision-making, professional practice, and patient safety [17], whereas the framework developed by the Association of Faculties of Pharmacy of Canada (AFPC) focuses on alignment and integration with pharmacy degree education [18]. As pharmacy practice continues to evolve, international pharmacist organizations have also provided clinical practice guidelines or recommendations relevant to ATMPs, translating competency expectations into specific professional actions and decision-making practices in clinical settings [19]. Notable examples include the European Association of Hospital Pharmacists’ recommendations on the handling of gene therapy medicinal products (GTMPs) [20]. Similarly, CFs for other HCPs, such as the CanMEDS framework for physicians and the Nursing Council of New Zealand competencies, demonstrate how contextual factors (e.g. population health priorities, service delivery models, and workforce expectations) influence the design and application of CFs [21]. These differences underscore that CFs are not “one-size-fits-all,” but must be tailored to the local healthcare context to ensure relevance and effectiveness.

In recent years, the application of ATMPs in hospital settings has increased globally, particularly in the treatment of cancers, rare diseases, and personalized medicine. Even in countries without locally approved ATMPs, patient access can be enabled through multinational clinical trials and regulatory pathways, such as the European Medicines Agency’s “hospital exemption” (Article 28 of Regulation (EC) No 1394/2007), which allows certain ATMPs to be prepared on a non-routine basis and used in a hospital for an individual patient under a physician’s responsibility within the same Member State. For example, the autologous CAR-T product ARI-0001 (varnimcabtagene autoleucel) has been authorized for clinical use in Spain via the hospital exemption pathway for specific eligible patients under national oversight [22]. However, in many emerging markets, the uptake of ATMPs has outpaced the development of dedicated regulatory frameworks, a suitably trained workforce, sophisticated manufacturing capacity, coordinated logistics and advanced healthcare facilities, all of which often remain limited [23, 24]. These gaps are tightly interlinked, as effective ATMP governance in hospitals relies on workforce capability to translate regulatory and technique requirements into validated workflows across the healthcare delivery [4]. When workforce readiness is insufficient, these measures may be implemented inconsistently across process steps, undermining the maintenance of auditable standard operating procedures (SOPs) and deviation control, and thereby increasing operational variability and patient-safety risks.

The Macao Special Administrative Region (SAR), as part of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), provides a relevant and informative setting for this study because it is featured with rapid introduction of innovative therapies, including ATMPs, within an evolving regulatory environment and ongoing efforts to develop high-end healthcare services [25]. Regulatory decision-making about ATMPs is primarily based on secondary evaluation, drawing on the decisions of more advanced regulatory systems in the pre-selected reference countries or jurisdictions. This approach allows faster entry to the local market for certain ATMPs. In this context, ATMP approval and commercialization have progressed rapidly in Macao, with three chimeric antigen receptor T-cell (CAR-T) products now available on the local market [26–28]. However, the local regulatory framework, institutional systems, and workforce readiness required for the safe and compliant use of ATMPs are still developing. This reflects a broader challenge in smaller and emerging-market healthcare systems, where access to innovation may outpace local implementation capacity. In addition, hospital pharmacists in Macao currently lack a standardized set of competencies tailored to the management and clinical use of ATMPs. Therefore, this study aims to develop a CF for hospital pharmacists managing ATMPs in emerging market settings, using Macao as the study setting to contextualize CF development and content-validation. The findings are expected to offer evidence-based insights that will facilitate the safe and effective integration of ATMPs into clinical practice, strengthen workforce competency development, and inform institutional decision-making in this emerging field.

Methods

We adopted a modified Delphi process using the RAND Corporation/University of California Los Angeles (RAND/UCLA) Appropriateness Method to develop the consensus-based CF for hospital pharmacists in managing ATMPs in Macao. The study was conducted and reported in accordance with the ACcurate COnsensus Reporting Document (ACCORD) reporting guideline [29–31]. The study protocol was prospectively registered on February 17, 2025, on the Open Science Framework (DOI: 10.17605/OSF.IO/B36ZT), and ethical approval was obtained from the Research Committee of the University of Macau (Approval ID: HE-0132-2024).

Study design

The RAND/UCLA Appropriateness Method was adopted to guide the process of consensus development considering that the clinical implementation of ATMPs requires consensus on complex care pathways under conditions of rapidly evolving and often limited evidence. In this context, the RAND/UCLA method provides a structured and auditable way to integrate evidence with expert judgment and to quantify agreement and disagreement across panelists, while incorporating a structured discussion between rating rounds to resolve divergent interpretations of statements. The suitability of this approach for ATMPs and other high-uncertainty clinical areas where evidence gaps limit purely evidence-driven recommendations has been demonstrated in recent consensus work [31]. For example, a consensus on the management of patient with multiple myeloma receiving CAR-T cell therapy employed a modified RAND/UCLA two-round Delphi process involving eight hematologists across Australia [32]. Similar approaches have also been used to harmonize practice recommendations across centers in cell and gene–adjacent settings, supporting its relevance when substantial inter-center variability is expected [33, 34].

In this study, we adapted the RAND/UCLA approach by embedding its rating principles within a modified Delphi process, applying them specifically to the development of a CF rather than to clinical appropriateness criteria. Specifically, competencies were rated using a nine-point scale across two iterative rounds, and agreement was assessed using the disagreement index (DI), enabling a transparent, reproducible, and auditable decision process [35, 36]. This approach supports methodological rigor and internal consistency in the resulting consensus-based CF.

To enhance transparency and methodological quality, the study was conducted and reported in accordance with the ACCORD guideline. ACCORD is the first reporting guideline specifically designed to support the rigorous and standardized reporting of consensus methods in biomedical research and clinical practice [29–31]. It promotes comprehensive disclosure of study materials, expert panel composition, and operational procedures, enabling readers to assess the credibility, transferability, and applicability of the study findings and recommendations. The consensus development process comprised several sequential steps: 1: Panelist selection; 2: Literature review and generation of draft CF; 3: Delphi process; 4: Analysis of results; and 5: Consensus finalization.

Selection of panel members

A pharmacist expert panel was assembled across the GBA to capture cross-jurisdictional and cross-role perspectives within hospital pharmacy practice. Panelists included senior hospital pharmacists and pharmacy managers from major hospitals in Macao, Hong Kong, and Guangdong, as well as pharmacists with health-system administrative and hospital management responsibilities. This composition was considered particularly relevant because pharmacists in these roles are directly involved in the implementation, oversight, and translation of pharmacy services and ATMP management within hospital settings [7]. Their practical insights helped ensure that the CF reflected real-world clinical and operational considerations. The panel members were responsible for reviewing, commenting on, rating the CF items, and engaging in discussions to establish and confirm the final consensus-based CF, which included the main CF and an accompanying evidence and elaboration (E&E) document.

The recruitment process was iterative and purposive. Potential panelists were initially identified through professional networks and expert recommendations to ensure coverage across the GBA and representation of key practice settings and roles. Additional members were invited as needed to address gaps in expertise and maintain balanced representation. Eligible candidates were invited via email, with follow-up reminders sent to non-respondents. Ultimately, 15 experts from the GBA were recruited, including senior hospital pharmacists and pharmacy administrators from major hospitals in Macao SAR, Hong Kong SAR, and Guangdong Province. All participating panelists were acknowledged as contributors in the final CF with their consent.

Consensus development

Literature review and development of preliminary CF

A systematic literature review was conducted to identify the critical roles of hospital pharmacists in providing interventions for contemporary advanced therapies and ATMPs [7]. This review systematically included studies published between 1 January 2013 and 30 April 2023 across four databases (PubMed, ScienceDirect, Web of Science, Scopus), yielding 34 publications that addressed pharmacists’ involvement in areas such as procurement, prescribing influences, preparation and delivery, administration, medicines use monitoring, and workforce training and development. In addition, nine relevant international guidelines were identified, including those from the Specialist pharmacy service (SPS) funded by the National Health Service (NHS) in the United Kingdom [37], and the EAHP to capture current recommendations on the pharmacy management of ATMPs [20].

Findings from the literature review, existing guidelines, and expert opinions were synthesized to develop a preliminary CF for the Delphi consensus process (Supplementary file). Specifically, evidence from the literature review and expert consultations was mapped against the Basel Statements on Hospital Pharmacy Practice [38], which provided a structured lens to categorize pharmacists’ activities across key domains of ATMP management. Meanwhile, the international guidelines offered governance references that complemented the empirical evidence from the review. Collectively, these sources informed the construction of the preliminary CF by defining essential intervention categories and outlining the potential functions and competencies of hospital pharmacists in the management of ATMPs. To confirm the absence of an existing CF for hospital pharmacists in ATMP-related practice, an updated supplementary literature search was conducted in February 2025 (one month before the start of the Delphi process) across PubMed and Google Scholar using combinations of terms related to “ATMPs”, “hospital pharmacists”, and “competency frameworks”. No relevant published CF was identified.

Two authors (COLU and JS) reviewed the draft CF to eliminate redundancy and refine items with unclear or ambiguous wording, ensuring that each item was unique, well-defined, and suitable for consensus evaluation. Discrepancies between authors were resolved through discussion. A structured Excel extraction table was used to organize and manage the CF items. Survey materials were initially developed by COLU and JS in both English and Chinese, followed by pilot testing. Based on feedback gathered during the pilot phase, revisions were made to the content clarity and user experience.

Delphi process

A structured Delphi methodology, based on the RAND/UCLA Appropriateness Method [39, 40], was employed to reach consensus on the items for inclusion in the reporting CF. The process comprised two iterative rounds. The Delphi rounds were administered via the Qualtrics Online Survey platform, which enabled automatic participant coding and anonymized submission of item ratings. Only aggregated results and de-identified feedback were shared with panelists between rounds to minimize dominance bias.

• Round one: In March 2025, panelists who consented to participate received an information pack containing an invitation letter, a participant information statement, an adult informed consent form. During registration, panelists were required to complete a preliminary survey to collect baseline data on their experience, geographical distribution, and demographic characteristics.

An online briefing session was held to introduce the research background and explain the Delphi process. Subsequently, panelists received an anonymous online survey via Qualtrics, which included 53 preliminary CF items. Each item was rated on a nine-point scale, with scores categorized as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Panelists were encouraged to suggest revisions to item wording, propose deletions, or identify missing items based on their expertise while completing the survey, including recommendations to clarify scope of practice, professional role boundaries, and the potential involvement of supporting personnel whenever relevant.

• Round two: In July 2025, a virtual consensus meeting was held to discuss the rating results from Round one and to re-rate each item, including any potential additional item. Prior to the meeting, each panelist received a summary of the first-round results, which included the frequency distribution of ratings on the nine-point scale, the overall median score for each item, and the compiled panelist comments along with the corresponding item revisions with responses. Individual ratings from other panelists were not disclosed.

Based on panelists’ ratings, agreement or disagreement was determined for each Round one item. During the second round, discussions mainly focused on remaining areas of disagreement and the wording clarity to refine statements and determine whether consensus could be achieved. All items were discussed regardless of agreement status, and panelists were given the opportunity to revise their ratings. All wording modifications were systematically documented.

Data collection and management

Upon receipt of completed rating sheets from panelists, quantitative ratings were tabulated and free-text comments were exported for analysis. Qualitative feedback was synthesized using a pragmatic content-analysis approach. Comments were first collated by item and then coded into recurrent themes. Two authors (COLU, JS) reviewed qualitative feedback from panelists and integrated them into proposed item-level revisions. Any discrepancies were discussed and resolved through consensus among all authors. Semantic adjustments were made to improve item clarity and concision where necessary.

For every item, the 30th and 70th percentiles adjusted for symmetry were calculated, as symmetric distributions around the midpoint require a narrower interpercentile range (IPR) to indicate disagreement compared with asymmetric distributions. Agreement was defined as cases where the symmetry-adjusted IPR (IPRAS) exceeded the IPR [34]. To facilitate interpretation of the ratings, a disagreement index (DI = IPR / IPRAS) was calculated and presented during the meeting, where DI > 1 indicating disagreement and DI ≤ 1 indicating consensus.

Predefined decision rules were applied to guide item retention, revision, or elimination. Items were retained when they achieved consensus (DI ≤ 1) and the central tendency of ratings indicated appropriateness (median ≥ 7). Items were revised when qualitative feedback suggested ambiguity, overlap, or context-specific adaptations were needed, or when ratings indicated uncertainty/disagreement (median 4–6 and/or DI > 1). Revised items were re-rated in the subsequent round. Items were eliminated when consensus indicated inappropriateness (median ≤ 3 with DI > 1) or when an item remained inappropriate after revision and re-rating [39].

Statistical analysis

All collected data were analyzed to assess the degree of consensus among participants. Descriptive statistics, including frequencies, percentages, means, standard deviations, and medians, were used to summarize participants’ ratings and responses. Demographic data and rating scores were presented as the mean and 95% confidence intervals (CIs). Consensus content-validation and decision-making regarding item retention, revision, or exclusion followed the criteria of the RAND/UCLA Appropriateness Method. Median scores, IPR, and IPRAS were calculated using SPSS Version 20. Audio recordings of the panel discussion (obtained with prior consent) were used for verification and qualitative synthesis.

To further evaluate the reliability and stability of the consensus, Cronbach’s α coefficient and the authority coefficient (Cr) were employed [41, 42]. Cronbach’s α was computed to assess the internal consistency of the CF, with α ≥ 0.7 considered acceptable. The Cr was applied to measure the credibility of expert judgments, calculated as Cr = (Cs + Ca)/2, where Cs represents self-reported familiarity with the items and Ca denotes the basis of judgment. The scoring range was derived from the Expert Consensus on Core Competency Framework of Chinese Clinical Pharmacist, with detailed values shown in Table 1 [43]. A Cr ≥ 0.7 was regarded as indicating sufficient authority of the panelists. Missing data were assessed at the round and item levels. In the event that any panelist did not provide ratings in each round, analyses for that round were conducted using the available responses from the participating panelists, and no imputation was performed.

Table 1.

Judgement criterion and scores for Cs and Ca

	Judgment criterion	Judgment scores
Familiarity coefficient (Cs)	Degree of familiarity	Very familiar	Relatively familiar		Generally familiar	Not very familiar	Unfamiliar
		1	0.8		0.5	0.2	0
Judgment coefficient (Ca)	Degree of influence	High		Moderate		Low	None
	Practical experience	0.5		0.4		0.3	0
	Theoretical analysis	0.3		0.2		0.1	0
	Understanding of peers	0.15		0.15		0.15	0
	Insight	0.05		0.05		0.05	0.05

Results

Overall, the CF comprised 53 items organized into six domains and was developed through a two-round modified Delphi process. Qualitative feedback across both rounds mainly focused on clarifying pharmacists’ responsibilities and interprofessional boundaries, strengthening quality assurance and biosafety considerations, specifying key operational procedures, defining the role of pharmacy technicians, and ensuring feasibility within the Macao hospital context. The finalized CF outlines pharmacists’ responsibilities and expected practice competencies in ATMP governance and compliance, and pharmaceutical services across the hospital clinical pathway, including prescription evaluation, handling and storage, preparation processes, issue and transportation, as well as administration and monitoring.

Delphi panel demographics

In the first round of the Delphi survey, 15 panelists were invited, all of whom completed the questionnaire, yielding a 100% response rate. All 15 panelists also participated in the second round, but only 14 valid responses were received, resulting in a completion rate of 93.3%. Table 2 summarized the characteristics of all participants. All panelists had a professional background of pharmacist, aged between 26 and 60 years, and had a minimum of 4 years of professional experience. Panelists with over 20 years of practice accounted for 60% (n = 9) in the first round and 57.1% (n = 8) in the second round.

Table 2.

Demographics of the Delphi panelists in each voting round

Characteristic	Round 1 (n = 15) Mar 9 - May 8, 2025	Round 2 (n = 14) July 13–22 Aug, 2025
Gender, n (%)
Female	10 (66.67)	9 (64.29)
Male	5 (33.33)	5 (35.71)
Age, n (%)
≤ 25	0	0
26–30	1 (6.67)	1 (7.14)
31–40	4 (26.67)	3 (21.43)
41–50	6 (40.00)	6 (42.86)
51–60	4 (26.67)	4 (28.57)
61 or over	0	0
Current professional seniority, n (%)
Pharmacist	8 (53.33)	8 (57.14)
Hospital Pharmacy Administrators	7 (46.67)	6 (42.86)
Professional experience, n (%)
≤ 3	0	0
4–10	3 (20.00)	3 (21.43)
11–20	3 (20.00)	3 (21.43)
> 20	9 (60.00)	8 (57.14)
Highest educational level, n (%)
Bachelor	5 (33.33)	5 (35.71)
Master	8 (53.33)	7 (50.00)
PhD	2 (13.33)	2 (14.29)
Geographic location of current work, n (%)
Macao SAR	8 (53.33)	8 (57.14)
HK SAR	2 (13.33)	2 (14.29)
Mainland China	5 (33.33)	4 (28.57)

Among the panelists, eight were pharmacists from four major hospitals in Macau. Of these, one held an administrative position related to pharmacy at the Health Bureau of Macao, one served as a hospital administrator, and one was a managerial staff member within the hospital pharmacy department. Two pharmacists were from two public hospitals in Hong Kong, one of whom held a managerial role in the hospital pharmacy department. The remaining five pharmacists were from five different tertiary hospitals in Guangdong province, all of whom held managerial positions within their respective pharmacy departments.

Delphi results

After all panelists completed the first-round Delphi questionnaire, the measures of central tendency, IPR, and IPRAS were analyzed as shown in Table 3. The DI for all 53 items was found to be less than 1.0, indicating the absence of statistically defined disagreement, reflecting acceptable consistency of panelist ratings for the item. The detailed score distributions are presented in Appendix I.

Table 3.

Overview of results for the assessed items for Delphi rounds

No		Measure of central tendency (round 1, n = 15)							Measure of central tendency (round 2, n = 14)
	Short title	Median	Mean ± SD	Percentile		IPR	IPRAS	DI (A/D)	Median	Mean ± SD	Percentile		IPR	IPRAS	DI (A/D)
				30th	70th						30th	70th
A Governance and compliance
1	Policy and regulation	8.00	7.80 ± 1.11	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.79 ± 0.86	7.00	8.50	1.50	6.63	0.23 (A)
2	Institutional governance	8.00	7.93 ± 0.93	7.00	9.00	2.00	7.00	0.29 (A)	8.00	8.00 ± 0.93	7.00	9.00	2.00	7.00	0.29 (A)
3	ATMP safety committee	8.00	7.40 ± 1.50	6.80	8.20	1.40	6.25	0.22 (A)	8.00	7.71 ± 1.10	7.00	8.50	1.50	6.63	0.23 (A)
4	Pharmacy services standards	8.00	7.67 ± 1.35	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.93 ± 1.16	7.00	9.00	2.00	7.00	0.29 (A)
5	Financial governance requirements	7.00	6.20 ± 1.51	5.00	7.00	2.00	4.00	0.50 (A)	7.50	7.57 ± 1.35	7.00	9.00	2.00	7.00	0.29 (A)
6	Clinical trial registration	7.00	7.00 ± 1.37	6.00	8.00	2.00	5.50	0.36 (A)	7.50	7.71 ± 0.80	7.00	8.00	1.00	6.25	0.16 (A)
7	Clinical use authorization	8.00	7.67 ± 0.94	7.00	8.00	1.00	6.25	0.16 (A)	7.50	7.71 ± 0.80	7.00	8.00	1.00	6.25	0.16 (A)
8	Commercial agreement review	7.00	7.27 ± 1.44	6.00	9.00	3.00	6.25	0.48 (A)	7.50	7.43 ± 1.05	7.00	8.00	1.00	6.25	0.16 (A)
9	Patient selection procedures	8.00	7.47 ± 1.31	7.00	8.20	1.20	6.40	0.19 (A)	7.00	7.29 ± 1.28	7.00	8.00	1.00	6.25	0.16 (A)
10	Interprofessional collaboration	8.00	7.60 ± 1.25	7.00	8.20	1.20	6.40	0.19 (A)	7.50	7.43 ± 1.35	7.00	8.50	1.50	6.63	0.23 (A)
B Prescription evaluation
11	Protocol compliance review	9.00	8.73 ± 0.57	9.00	9.00	0.00	8.50	0.00 (A)	9.00	8.57 ± 0.73	8.50	9.00	0.50	8.13	0.06 (A)
12	Medication order review	8.00	7.93 ± 1.34	7.80	9.00	1.20	7.60	0.16 (A)	9.00	8.36 ± 0.81	8.00	9.00	1.00	7.75	0.13 (A)
13	Patient eligibility confirmation	8.00	7.80 ± 1.11	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.64 ± 1.54	7.00	9.00	2.00	7.00	0.29 (A)
14	Order-Procurement coordination	8.00	7.80 ± 1.22	7.00	9.00	2.00	7.00	0.29 (A)	8.00	8.07 ± 0.88	7.00	9.00	2.00	7.00	0.29 (A)
C Handling and storage
15	Handling & storage SOP compliance	9.00	8.33 ± 0.87	7.80	9.00	1.20	7.60	0.16 (A)	8.00	8.00 ± 1.13	7.50	9.00	1.50	7.38	0.20 (A)
16	Process monitoring	9.00	8.40 ± 0.80	8.00	9.00	1.00	7.75	0.13 (A)	8.00	7.86 ± 1.12	7.00	9.00	2.00	7.00	0.29 (A)
17	Material collection verification	8.00	7.60 ± 1.40	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.29 ± 1.22	7.00	8.00	1.00	6.25	0.16 (A)
18	Pharmacy receiving readiness	8.00	8.13 ± 0.96	7.80	9.00	1.20	7.60	0.16 (A)	8.00	7.93 ± 1.10	7.00	9.00	2.00	7.00	0.29 (A)
19	Coordination for off-site ATMPs	7.00	7.40 ± 1.40	6.80	9.00	2.20	6.85	0.32 (A)	7.00	7.07 ± 1.44	7.00	8.00	1.00	6.25	0.16 (A)
20	Cold storage equipment assurance	9.00	8.13 ± 1.02	7.00	9.00	2.00	7.00	0.29 (A)	8.50	8.21 ± 0.86	7.50	9.00	1.50	7.38	0.20 (A)
21	Alternative storage assessment	8.00	7.67 ± 1.30	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.29 ± 1.58	7.00	8.00	1.00	6.25	0.16 (A)
22	Cross-contamination control	8.00	8.00 ± 1.15	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.36 ± 1.63	7.00	8.50	1.50	6.63	0.23 (A)
23	Aseptic and biosafety operation	8.00	7.73 ± 1.18	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.64 ± 1.04	7.00	8.00	1.00	6.25	0.16 (A)
24	Expiry monitoring and alerts	9.00	8.33 ± 0.87	7.80	9.00	1.20	7.60	0.16 (A)	8.50	8.14 ± 1.12	8.00	9.00	1.00	7.75	0.13 (A)
25	Temperature monitoring	8.00	8.00 ± 1.15	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.79 ± 1.01	7.00	9.00	2.00	7.00	0.29 (A)
26	Alarm system and contingency planning	8.00	8.20 ± 0.83	7.80	9.00	1.20	7.60	0.16 (A)	8.00	8.00 ± 0.85	7.00	9.00	2.00	7.00	0.29 (A)
27	ATMP handling & storage training	9.00	8.40 ± 0.80	8.00	9.00	1.00	7.75	0.13 (A)	9.00	8.36 ± 0.81	8.00	9.00	1.00	7.75	0.13 (A)
D Preparation processes
28	Preparation SOP compliance	8.00	8.20 ± 0.83	7.80	9.00	1.20	7.60	0.16 (A)	8.00	7.79 ± 1.08	7.00	8.50	1.50	6.63	0.23 (A)
29	GMSC safety risk assessment	8.00	7.67 ± 1.01	7.00	8.20	1.20	6.40	0.19 (A)	7.00	7.50 ± 0.73	7.00	8.00	1.00	6.25	0.16 (A)
30	ATMP thawing and preparation	8.00	7.87 ± 0.96	7.00	9.00	2.00	7.00	0.29 (A)	7.00	7.71 ± 0.88	7.00	8.50	1.50	6.63	0.23 (A)
31	Aseptic preparation supervision	8.00	7.93 ± 0.93	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.71 ± 1.10	7.00	8.50	1.50	6.63	0.23 (A)
32	Lab-to-Clinic transport monitoring	7.00	7.47 ± 1.02	7.00	8.00	1.00	6.25	0.16 (A)	7.00	6.93 ± 1.39	6.00	8.00	2.00	5.50	0.36 (A)
33	Outsourced service management	8.00	7.53 ± 1.31	6.80	9.00	2.20	6.85	0.32 (A)	7.00	7.50 ± 1.18	7.00	8.50	1.50	6.63	0.23 (A)
34	Personal protective equipment	9.00	8.40 ± 0.80	8.00	9.00	1.00	7.75	0.13 (A)	8.00	7.86 ± 0.83	7.00	8.50	1.50	6.63	0.23 (A)
35	Aseptic waste management	8.00	7.93 ± 1.29	7.80	9.00	1.20	7.60	0.16 (A)	7.50	7.79 ± 0.86	7.00	8.50	1.50	6.63	0.23 (A)
36	Pre-treatment requirements	7.00	7.00 ± 1.9	6.00	8.20	2.20	5.65	0.39 (A)	8.00	7.93 ± 0.88	7.00	9.00	2.00	7.00	0.29 (A)
37	Billing coordination	7.00	6.87 ± 1.15	6.00	7.00	1.00	4.75	0.21 (A)	7.50	7.64 ± 0.72	7.00	8.00	1.00	6.25	0.16 (A)
38	ATMP preparation training	9.00	8.27 ± 0.85	7.80	9.00	1.20	7.60	0.16 (A)	8.50	8.29 ± 0.80	8.00	9.00	1.00	7.75	0.13 (A)
E Issue and transportation processes
39	Issue & transportation SOP compliance	8.00	8.20 ± 0.83	7.80	9.00	1.20	7.60	0.16 (A)	7.50	7.79 ± 0.86	7.00	8.50	1.50	6.63	0.23 (A)
40	Clinical area transportation	8.00	7.53 ± 1.75	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.79 ± 1.01	7.00	9.00	2.00	7.00	0.29 (A)
41	Pharmacy-approved clinical worksheet	8.00	7.27 ± 1.69	7.00	8.20	1.20	6.40	0.19 (A)	8.00	7.93 ± 0.88	7.00	9.00	2.00	7.00	0.29 (A)
42	Optimized ATMP transport planning	8.00	7.53 ± 1.36	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.57 ± 1.18	7.00	8.50	1.50	6.63	0.23 (A)
43	Clinical handover coordination	8.00	7.87 ± 1.09	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.64 ± 1.11	7.00	8.50	1.50	6.63	0.23 (A)
44	Final treatment verification	8.00	7.87 ± 1.2	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.86 ± 1.12	7.00	9.00	2.00	7.00	0.29 (A)
45	ATMP transportation training	8.00	8.13 ± 0.88	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.86 ± 0.83	7.00	8.50	1.50	6.63	0.23 (A)
F Administration and monitoring
46	Clinical medication management	9.00	8.33 ± 0.79	8.00	9.00	1.00	7.75	0.13 (A)	8.50	8.14 ± 0.91	7.00	9.00	2.00	7.00	0.29 (A)
47	ATMP waste disposal protocols	8.00	7.93 ± 1.24	7.00	9.00	2.00	7.00	0.29 (A)	8.00	7.71 ± 1.22	7.00	9.00	2.00	7.00	0.29 (A)
48	ATMP resource access and HCP training	8.00	7.80 ± 0.98	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.64 ± 1.04	7.00	8.50	1.50	6.63	0.23 (A)
49	Clinical decision support	8.00	8.27 ± 0.77	8.00	9.00	1.00	7.75	0.13 (A)	8.00	8.00 ± 0.85	7.00	9.00	2.00	7.00	0.29 (A)
50	Continuity of care coordination	7.00	7.47 ± 1.31	7.00	9.00	2.00	7.00	0.29 (A)	7.50	7.57 ± 1.29	7.00	9.00	2.00	7.00	0.29 (A)
51	Efficacy and safety monitoring	8.00	8.20 ± 0.83	7.80	9.00	1.20	7.60	0.16 (A)	8.00	7.93 ± 1.03	7.00	9.00	2.00	7.00	0.29 (A)
52	Long-term follow-up planning	8.00	7.60 ± 1.45	7.00	8.20	1.20	6.40	0.19 (A)	7.00	7.57 ± 1.05	7.00	8.50	1.50	6.63	0.23 (A)
53	Patient counseling and education	9.00	8.33 ± 0.79	8.00	9.00	1.00	7.75	0.13 (A)	8.00	8.00 ± 0.93	7.00	9.00	2.00	7.00	0.29 (A)

Consensus was consistently achieved across all six domains. However, the extent of wording refinement differed by domain. Appendix II lists the amendments made by panel to the original criteria, as well as the justifications for these revisions. Of the 53 items, 33 (62.3%) were proposed for revision despite having achieved consensus on their appropriateness. The research team revised these items accordingly to produce the second-round Delphi questionnaire for re-rating. In the second round, valid responses were obtained from 14 panelists. Based on the feedback, 9 items were further refined, while 44 items were accepted without any change. The final consensus CF comprised six domains encompassing 53 items: (A) Governance and compliance (Items No.1–10, n = 10); (B) Prescription evaluation (No. 11–14, n = 4); (C) Handling and storage (No. 15–27, n = 13); (D) Preparation processes (No.28–38, n = 11); (E) Issuance and transportation (No. 39–45, n = 7); and (F) Administration and monitoring (No. 46–53, n = 8).

Feedback from the two rounds of Delphi surveys provided critical input for refining the consensus-based CF (Appendix II). Panelist opinions primarily focused on the scope of hospital pharmacists’ responsibilities in ATMPs management, including their participation in ATMPs Safety Committees (n = 2) and their roles in financial governance and approval procedures (n = 3), coordination of drug procurement (n = 2), and review of commercial agreements (n = 1).

Regarding the delineation of institutional and individual responsibilities, some panelists noted that the registration and progress tracking of ATMPs clinical trials (n = 3), as well as the application for and monitoring of clinical-use licenses (n = 3), should primarily be handled by sponsors or administrative departments. Pharmacists, however, are expected to provide pharmaceutical support, assist in supervision, and facilitate communication throughout these processes.

In terms of quality control, experts recommended further refinement of requirements related to ATMP expiry management (n = 2) and continuous temperature monitoring (n = 2). For dispensing and transportation processes, three panelists suggested that pharmacists should assist in developing and managing medication administration records and guide nursing staff in accurate documentation. Additionally, three panelists proposed that trained pharmacy technical assistants in Macao could assist selected ATMP-related technical operations under the supervision of pharmacists (Items No. 6,7,15,28,39) to improve work efficiency. Within this CF, pharmacists retained ultimate clinical accountability, while technicians’ roles were limited to supportive, protocol-driven logistical and operational assistance as directed by the supervising pharmacist.

To assess the internal consistency of the CF, reliability analyses were conducted for both Delphi rounds. The Cronbach’s α coefficients were 0.975 and 0.979 for the first and second rounds, respectively, demonstrating excellent internal consistency. The panelist Cr ranged from 0.50 to 1.00 in the first round and 0.40-1.00 in the second round, with mean values of 0.70 in both, indicating an acceptable level of expert credibility. Detailed scoring for each expert’s familiarity with the items and their judgmental basis is provided in the Appendix III.

Discussion

This study helps bridge an important evidence gap by systematically developing a practice-oriented, role-based CF for hospital pharmacists involved in ATMP management in an emerging-market context. The finalized CF provides a structured and context-specific appropriateness tool for defining pharmacists’ expected roles and practice requirements in relation to ATMP governance, compliance, and service delivery within hospital settings (Table 4). In doing so, it offers practical support for the safe, effective, and compliant use of ATMPs in the Macao healthcare system, while serving as a foundation for pharmacist workforce development and continuing professional preparation in response to the rapidly evolving ATMP landscape.

Table 4.

CF for hospital pharmacist managing ATMPs in Macao

No.	Domain and competency statement
A	Governance and compliance
1	Hospital pharmacists are expected to possess knowledge of Macao’s ATMP policies, regulations, and institutional management standards to ensure the compliance and expandability of their pharmaceutical services.
2	Hospital pharmacists are expected to participate in the establishment of ATMP management bodies within their institutions, contribute to the development of management standards (including evaluation, procurement, receipt, preparation, storage, pre-use procedures, transport, financial management, and approval processes), and engage in their regular monitoring, assessment, and optimization.
3	Hospital pharmacists are expected to participate in relevant institutional committees related to ATMPs (e.g., the Genetic Modification Safety Committee [GMSC] or Ethics Committee), engage in technical safety risk assessment and ethical review, and assist in developing or implementing appropriate control measures (as applicable).
4	Hospital pharmacists are expected to lead the development of institutional standards for ATMP-related pharmaceutical services to support appropriate allocation of human resources and training requirements.
5	Hospital pharmacists are expected to participate in institutional discussions on ATMP supply, cost assessment, and economic accessibility, in order to support the development of financial management and approval strategies aligned with clinical needs (as applicable).
6	Hospital pharmacists should are expected to contribute pharmaceutical support, as required by the sponsor or institution, to assist in ensuring the accuracy of application materials during the submission and tracking of ATMP clinical trial registration applications to the relevant authorities; pharmacy technicians may also participate in such support activities when needed (as applicable).
7	Hospital pharmacists are expected to participate in the submission and tracking of ATMP clinical use approval applications to the relevant authorities, as required by the sponsor or institution, to assist in ensuring product accessibility; pharmacy technicians may also be involved in such support activities when needed (as applicable).
8	Hospital pharmacists are expected to participate in the review of commercial agreements on ATMPs signed between their institutions and relevant pharmaceutical companies, providing professional input on pharmaceutical-related clauses to ensure alignment with professional standards and patient interests (as applicable).
9	Hospital pharmacists are expected to possess knowledge of the patient selection procedures for ATMP use within their institutions and assist the medical team in assessing patient eligibility.
10	Hospital pharmacists are expected to contribute to the establishment of effective communication and collaboration mechanisms between their institutions, relevant authorities, and healthcare professionals, to safeguard the continuity and stability of ATMP supply and to promptly address any issues arising in the management process when needed.
B	Prescription evaluation
11	Hospital pharmacists are expected to review medical orders against standard treatment guidelines and institutional ATMP treatment protocols to ensure their appropriateness.
12	Hospital pharmacists are expected to assess the rationality and safety of medical orders, based on patients’ medical records and medication information, to support treatment decisions for patients, particularly in referral situations.
13	Hospital pharmacists are expected to assist in assessing that patients meet the treatment standards for ATMPs and that all pharmaceutical-related requirements are fulfilled prior to therapy.
14	Hospital pharmacists are expected to verify coordination between medical orders and pharmaceutical procurement needs, and to accurately carry out operations such as preparation and dispensing of prescribed medicines in the hospital information system, to ensure compliance and accessibility of medicine supply (as applicable).
C	Handling and Storage
15	Hospital pharmacists are expected to comply with the management standards for the manufacturing, receipt, handling, storage, and disposal processes of different types of ATMPs, and participate in the development of corresponding standard operating procedures (SOPs). Under the hospital’s internal management standards, trained pharmacy technicians may assist pharmacists in tasks such as the receipt, handling, and storage of ATMPs.
16	Hospital pharmacists are expected to oversee the processes for receiving, handling, storing, and disposing of different types of ATMPs in compliance with regulations, and to perform regular monitoring and detailed documentation to ensure that product viability, storage temperature, and conditions meet relevant standards.
17	Within the scope of management involving the pharmacy department, hospital pharmacists are expected to assist in verifying that the collection of autologous and allogeneic ATMP preparation materials in their institutions is approved by the relevant competent authorities, in order to guarantee the legality and reliability of the materials (as applicable).
18	Hospital pharmacists are expected to verify that the pharmacy receiving area is equipped with the capabilities for handling dry ice, thawing ATMPs, and performing aseptic operations, in order to properly receive and temporarily store those ATMPs suitable for pharmacy handling.
19	For ATMPs that are usually not handled in the pharmacy (e.g., in stem cell laboratories), hospital pharmacists are expected to participate in coordination and support the work of other relevant departments within their institutions, to ensure that the processes of product receipt, storage, preparation, dispensing, and disposal comply with institutional regulations.
20	Hospital pharmacists are expected to verify that the pharmacy is equipped with the necessary frozen storage facilities, determine the optimal storage location according to the storage temperature and duration requirements of different types of ATMPs, and ensure that the storage equipment functions properly to prevent product quality degradation.
21	If the pharmacy lacks equipment that meets storage conditions, hospital pharmacists are expected to participate in evaluating the feasibility of using a stem cell laboratory, either under pharmacy supervision or outsourced, as an alternative storage solution, and conduct corresponding risk assessments to select an appropriate storage and transportation method.
22	Hospital pharmacists are expected to support the implementation of isolation procedures based on product characteristics when receiving, handling, and storing cell-based ATMPs, and to take necessary measures to reduce the risk of cross-contamination (as applicable).
23	Hospital pharmacists are expected to support the adherence to aseptic operation standards during the receipt, handling, and storage of gene therapy products, and to take necessary measures to prevent accidental release of gene vectors and the risk of environmental exposure (as applicable).
24	If ATMPs are stored in the pharmacy, hospital pharmacists are expected to conduct comprehensive monitoring of their shelf life and establish data recording and alert mechanisms to prevent product expiration and loss of efficacy, with strengthened management for products with short expiry periods.
25	Hospital pharmacists are expected to conduct continuous monitoring of ATMPs’ temperature throughout the process from receipt and storage to before administration, establish a data recording system, and develop emergency response plans for temperature deviations or abnormal conditions.
26	Hospital pharmacists are expected to support the installation of a temperature alarm system suitable for ATMPs in the pharmacy, and to develop emergency plans and response measures, and regularly organize and participate in scenario simulations and emergency drills (e.g., cold-chain equipment failure or prolonged power outage). In the event of temperature abnormalities, hospital pharmacists are expected to take corrective actions based on the risk assessment in the SOP, and complete records for subsequent traceability and improvement.
27	Hospital pharmacists are expected to receive appropriate training and acquire professional knowledge and skills in the receipt, handling, and storage of ATMPs, in order to accurately determine whether products meet requirements, and be able to promptly identify and address any potential problems.
D	Preparation processes
28	Hospital pharmacists are expected to adhere to management standards for ATMP preparation processes and, according to the Summary of Product Characteristics (SmPC) of different ATMP types or the requirements of clinical trial protocols, contribute to the development of SOPs for thawing, aseptic preparation, and transportation prior to ATMP use. Under the hospital’s internal management regulations, trained pharmacy technicians may assist pharmacists in the preparatory tasks of thawing, preparation, and transportation required before ATMP use.
29	In cases involving the Gene Modification Safety Committee (GMSC) conducting safety risk assessments of gene therapy products, hospital pharmacists are expected to participate in the evaluation process to ensure compliance in subsequent operations.
30	Hospital pharmacists are expected to perform preparatory procedures such as thawing, preparation, or reconstitution, prior to the use of ATMPs according to their specific characteristics, and to comply with the relevant SOPs, SmPC, or clinical trial protocol requirements.
31	Hospital pharmacists are expected to oversee the aseptic preparation and operational processes of ATMPs, and to maintain transportation management of ATMPs within aseptic preparation areas complies with relevant SOPs, SmPC, or clinical trial protocol requirements (as applicable).
32	If the thawing and aseptic processing of ATMPs need to be conducted in a stem cell laboratory, hospital pharmacists are expected to oversee the process of transporting the products from the stem cell laboratory to the clinical area. When necessary, pharmacists may request relevant departments to provide transport records or related documentation to ensure patient medication safety.
33	If outsourced services involve aseptic storage and handling of ATMPs, hospital pharmacists are expected to review and verify the technical agreements with the outsourcing service providers, to confirm that the agreements clearly define the responsibilities, obligations, operating procedures, and quality standards of both parties.
34	Hospital pharmacists are expected to support the provision of personal protective equipment (PPE), such as spill kits, when handling various types of ATMPs, to ensure their own safety.
35	Hospital pharmacists are expected to coordinate the management process of waste generated after aseptic preparation, to ensure that such waste is handled safely and in compliance with regulations.
36	Hospital pharmacists are expected to assist the medical team in completing the necessary pretreatments required before ATMP therapy, and to provide pharmaceutical support and medication consultation to support standards-compliant medication-related preparation for patients prior to ATMP therapy.
37	Hospital pharmacists are expected to coordinate communication between the pharmacy and relevant departments, assist in confirming ATMP medication information and booking requirements, and provide treatment-related parameters to support subsequent billing processes.
38	Hospital pharmacists are expected to possess the knowledge and skills required for aseptic preparation and transportation of ATMPs, including aseptic techniques, personal protection, and emergency handling, in order to carry out preparatory procedures safely and correct and correctly.
E	Issue and transportation processes
39	Hospital pharmacists are expected to adhere to management standards for the routine receipt of ATMPs in the pharmacy, and to contribute to the development of pharmacy SOPs for the transport of ATMPs from the pharmacy to clinical areas, as well as for product thawing, dispensing, and receipt. Under the hospital’s internal management regulations, trained pharmacy technicians may assist pharmacists in tasks related to the transport of ATMPs from the pharmacy to clinical areas, and in product thawing, dispensing, and receipt.
40	Hospital pharmacists are expected to participate in coordinating the transport, thawing, dispensing, and receipt of ATMPs in clinical areas, and to assist in maintaining compliance of operations comply with relevant SOPs, SmPC, or clinical trial protocol requirements.
41	Hospital pharmacists are expected to assist in developing and using pharmacy-approved clinical medication record forms, tailored to the characteristics of different ATMPs, providing pharmaceutical guidance on usage and dosage, administration time, and special precautions, to support treatment safety and accuracy.
42	Before transporting ATMPs from the pharmacy to clinical areas, hospital pharmacists are expected to plan and determine the optimal transport route and method according to product characteristics, and to oversee the entire process of product delivery to the clinical area.
43	Hospital pharmacists are expected to coordinate effective handover with other clinical staff when ATMPs are received in clinical areas, communicate that the ATMPs’ special storage and handling requirements, and jointly verify the receipt information and sign for confirmation.
44	Hospital pharmacists are expected to re-verify patient information and treatment plans, and to check the dispensing process before patients ATMPs dispensing in order to ensure medication accuracy and safety.
45	Hospital pharmacists are expected to receive appropriate training in ATMP dispensing and clinical transport, and to demonstrate familiarity with the use of spill kits and personal protective equipment, in order to support safe practice and effective emergency response during dispensing and transport.
F	Administration & Monitoring
46	Hospital pharmacists are expected to participate in patients’ clinical medication management, providing professional guidance before, during, and after ATMP administration, as well as offering pharmaceutical advice on treatment-related toxicity management and contraindicated drugs.
47	Hospital pharmacists are expected to possess knowledge of the special operating procedures for managing ATMP-related discharges, and to oversee waste disposal processes for viral vectors or cellular materials comply with relevant regulations.
48	Hospital pharmacists are expected to support the availability of ATMP-related resources, coordinate to enable the medical team to access the SmPC, clinical trial protocols, and relevant investigator manuals in a timely manner, and provide necessary guidance and training for relevant healthcare professionals.
49	Hospital pharmacists are expected to participate as key members of the medical team or ATMPs clinical group in clinical decision-making, and to provide professional advice to support the development of specific clinical guidelines.
50	Hospital pharmacists are expected to proactively coordinate multi-channel communication pathways and maintain communication with healthcare professionals from referral centres, primary care institutions, and other facilities, to support continuity and coordination of patient treatment.
51	Hospital pharmacists are expected to monitor drug efficacy and safety during ATMP use, and to develop detailed monitoring plans to promptly identify and manage potential adverse reactions, thereby safeguarding patient safety and treatment effectiveness.
52	Hospital pharmacists are expected to participate in the design and implementation of patients’ long-term follow-up plans, and to assist physicians by providing recommendations for medication adjustments based on patients’ clinical responses and monitoring results, in order to optimize treatment outcomes and medication safety.
53	Hospital pharmacists are expected to participate in patient consultations and provide pharmaceutical education to patients and their caregivers regarding ATMP treatment, potential side effects, drug interactions, and toxicity management.

This CF is intended as a consensus-based, practice-oriented reference for hospital pharmacists involved in ATMP management within the Macao context. It is not intended to define legally binding responsibilities or regulatory requirements. Future legal or regulatory developments may further clarify the scope of pharmacist involvement across hospital settings

Appropriateness tools specific for ATMPs

Building on the consensus-derived CF, this study provides an appropriateness tool that reflects the distinctive governance and management requirements of ATMPs within hospital settings. The strong retention of items across Delphi rounds may be explained by the rigorous pre-Delphi development process, whereby candidate items were generated from systematic evidence sources and preliminary expert input, leading to substantial baseline agreement on their relevance. In contrast to general CFs for pharmacists (e.g., the FIP GbCF, the ACCP clinical pharmacist CF), this ATMP-oriented CF consolidates pharmacy-relevant competencies that are required when pharmacists contribute to multidisciplinary ATMP care pathways. While general CFs emphasize broad domains such as clinical decision-making, professional practice, and patient safety, the CF presented in this study specifies competencies needed to implement ATMP governance and services in hospitals. These include pharmacists’ involvement in biosafety risk management, financial governance, specialized logistics, product receipt and storage, and long-term safety monitoring specific for ATMPs.

Biosafety risk management

Pharmacists’ involvement in institutional biosafety and ethics committees should be understood within the ATMP CF as supportive, practice-based contribution to multidisciplinary decision-making. In the current Macao context, where a dedicated regulatory framework for ATMPs has not yet been established, ethics-related review and approval processes remain largely hospital-based and internally governed. Within this setting, pharmacists’ involvement in biosafety and ethical review should be interpreted as supportive participation within a multidisciplinary process provided where needed, rather than as an independent or formally authorized review role.

Given that many gene and genetically modified (GMO) therapies rely on viral vectors for therapeutic delivery, biosafety concerns such as off-target infection, vector-related immune reactions, and potential viral shedding remain critical issues in clinical practice [44]. Establishing independent biosafety assessment procedures within hospital pharmacies, accompanied by protective and operational standards, has become a key consideration in mitigating risks associated with GMO medicines. Integrating viral vector risk classification and aligned biosafety levels (BSL) into these assessments may help minimize occupational exposure and environmental dissemination [45]. Strengthening pharmacists’ biosafety competence and regulatory awareness, and promoting their participation in institutional biosafety committees, could further support evidence-based handling and disposal of ATMPs.

By contributing pharmacological and toxicological evaluations during ethical review, pharmacists help assess the balance between therapeutic benefits and potential risks, evaluate the adequacy of risk disclosure in informed consent documents, and support the design of monitoring, reporting, and long-term follow-up plans. Such involvement not only strengthens patient safety but also reinforces the relevance of pharmacist engagement in multidisciplinary ATMP management [20, 46].

Financial governance

The distinctive cost profile and potentially curative nature of ATMPs have redefined conventional approaches to reimbursement and payment, drawing increasing attention from stakeholders involved in market access, including industry, regulators, hospital management, pharmacists, and patient advocacy groups [47]. Traditional payment models are poorly aligned with the long-term and uncertain clinical benefits of ATMPs, highlighting the need for adaptive frameworks that can balance innovation incentives with financial sustainability [48]. Outcome-based payment schemes have emerged as a promising approach, yet their successful implementation in healthcare institutions requires more than technical alignment on pricing structures or data systems [49]. It demands shared understanding of outcome definitions, transparent governance across stakeholders, and mechanisms for long-term patient follow-up and data verification [46, 50].

In Macao, specific reimbursement and payment regulations for ATMPs have not yet been established. Under such context, pharmacists, particularly those with administrative or managerial responsibilities, are well positioned to this process. Their involvement in institutional discussions on ATMP supply, cost assessment, and economic accessibility allows pharmacists to contribute professional insights to contractual reviews between hospitals and manufacturers, particularly on clauses related to pharmaceutical standards and patient safety. Such participation strengthens financial governance for ATMPs and supports the long-term affordability and sustainability of the healthcare system.

Specialized logistics and preparation

Handling ATMPs within hospital pharmacies requires pharmacists to maintain advanced competencies in aseptic technique, product traceability, and environmental control. Owing to their biological complexity and temperature sensitivity, every step from transportation and receipt to thawing, preparation, storage, and final disposal must follow validated procedures with continuous monitoring of critical parameters such as temperature and time [51, 52]. Pharmacists are responsible for ensuring product integrity and patient safety by maintaining an unbroken chain of identity and verifying compliance with manufacturer specifications, GMP standards, and regulatory requirements, including Qualified Person (QP) release and Certificates of Analysis (CoA) [52, 53].

How these responsibilities are translated into practice is illustrated by two professional models developed within the UK and French contexts [54, 55]. In the UK, the concept of point-of-care (POC) manufacturing readiness highlights the institutional maturity required for hospitals to produce ATMPs on site. The study reported by Bicudo and Brass described how NHS hospitals have progressively established GMP-compliant facilities, developed ATMP oversight committees, and integrated ISO-accredited laboratories to support activities such as cell handling, cryopreservation, and QP release. The framework envisions “control sites” coordinating multiple hospitals, with trained pharmacists and QPs ensuring batch certification even for ultra-short-lived therapies produced at bedside [54]. In contrast, the guidelines of the French Society for Oncology Pharmacy (SFPO) define a highly standardized pharmaceutical circuit for ATMPs, specifying procedures for product receipt by two authorized staff members, segregation of cryogenic storage, reconstitution in controlled-atmosphere cleanrooms, and validated inter-batch decontamination [55]. Together, these models exemplify evolving professional strategies that transform hospital pharmacies into integrated sites of advanced therapy preparation, quality assurance, and clinical delivery.

Long-term medication monitoring

ATMPs present unique safety profiles distinct from those of conventional therapies such as small molecules or monoclonal antibodies. In GTMPs, acute adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are frequently observed in CAR-T cell treatments [56]. For therapies employing integrating vectors or high-dose adeno-associated virus (AAV) vectors, the therapeutic genetic material itself (e.g. inserted genes, regulatory elements, and vector sequences) may trigger insertional mutagenesis, immunogenicity, off-target expression, or potential genotoxic effects. These risks require continuous and long-term safety monitoring. Meanwhile, the professional competence of pharmacists in ATMP management and long-term safety monitoring has gained growing recognition in clinical practice [7, 57]. By participating in the development and implementation of institutional Risk Management Plans (RMPs), coordinating the exchange of safety data among interdisciplinary team, and continuously tracking patient outcomes and adverse events, pharmacists can contribute to the early identification and mitigation of potential risks.

Capacity building for pharmacists

Evidence indicates that CFs are effective tools for promoting professional development and performance evaluation [58–60]. By applying this CF, pharmacists are expected to retain responsibility for ATMP-related governance, compliance, service delivery and coordination, whereas pharmacy technicians may support selected protocol-based technical or logistical tasks under pharmacist supervision. In addition, the adoption of CFs may also support workforce stability by fostering clinical pathways, reinforcing professional identity, and ultimately enhancing pharmacists’ job satisfaction and retention within increasingly complex and specialized healthcare settings [61]. Although competency-based approaches are increasingly emphasized in pharmacy education, meaningful improvement in patient safety and pharmacy performance can only be achieved when such frameworks are integrated into coherent structures of education, accreditation, performance assessment, and institutional support.

The ATMP-specific CF proposed in this study functions as a domain model that articulates “what competencies should be expected” for practice. It can also serve as a blueprint for the subsequent development of competency-based education and assessment tools [62]. In practice, each competency standards may be operationalized into observable behaviors and performance indicators, enabling the design of assessment content aligned with the intended behavioral domain. The CF provides a structured reference for external evaluation and continuing professional development (CPD), pharmacist credentialing, and performance appraisal. This approach offers strategic direction for establishing specialized ATMP pharmacist roles and workforce planning in Macao.

Building on this CF, future ATMP education and CPD programs are recommended to adopt a modular, competency-based, and practice-oriented design approaches. The curriculum could be divided into independent modules aligned with key competency domains, such as vector biology and immunogenicity, aseptic and cold-chain operations, safety monitoring and long-term follow-up, and regulatory or ethical governance. To strengthen accessibility, modules can specify learning outcomes and task-based competencies that map directly to the CF domains, with associated assessment methods (e.g., case-based questions, simulation checklists, workplace-based assessments) [63]. In addition, multimodal delivery, combining theory-based e-learning, hands-on simulation or on-site practice, and case-based workshops, aligns with international practices in ATMP training and helps bridge the gap between theoretical knowledge and performance. Experiences from the EMA and the UK NHS e-learning modules, have modeled this blended approach to ATMP workforce preparedness, demonstrating how modular curricula can remain current with evolving scientific and regulatory developments [64].

Meanwhile, performance assessment should be integrated with education and continuous quality improvement (CQI). Beyond initial certification, ongoing internal competency re-assessment, and practice audits and feedback loops are essential to maintain proficiency in low frequency but high-risk tasks. In operational terms, this requires translating the CF domains into assessment specifications, including clear descriptions of the behaviors assessed, the cognitive processes expected for selected-response items where applicable, and scoring rubrics for performance-based tasks [65]. Evidence suggests that structured competency assessments enhance pharmacists’ self-efficacy and reduce skill decay, supporting the establishment of systematic pre- and post-training evaluations and routine audits in ATMP practice [66].

In addition, future capacity building may benefit from a formal credentialing and role-tiering mechanism that distinguishes core (essential) from advanced (expanded) competencies, offering practical value for workforce planning. The study by Engle et al. reported that core competencies emphasize fundamental requirements for patient and product safety (e.g., aseptic technique, cold-chain management, and safety monitoring), whereas advanced competencies may extend to governance-related domains such as ethics review, financial negotiation or health technology assessment [67]. Such tiering clarifies role expectations and enables structured training with progressive certification, which holds particular relevance for smaller yet steadily developing healthcare systems such as Macao’s. Future iterations of the CF could formally embed this structure to guide resource allocation and support research evaluating feasibility and impact.

Strengths and limitations

This study developed a CF that is explicitly aligned with the distinctive characteristics of ATMPs and the hospital practice context of Macau. In the absence of local ATMP-specific regulatory tools or clinical practice guidelines, this CF helps fill an institutional gap by providing a structured reference for hospitals to establish internal procedures for the safe and appropriate use of ATMPs and by offering a systematic foundation for multidisciplinary collaboration. A further strength is the inclusion of pharmacy experts from the GBA, which was a deliberate methodological choice to enhance the representativeness and potential transferability of the CF. The three jurisdictions differ in their maturity of ATMP regulation, healthcare systems, and clinical implementation. Given that Macao remains in the early adoption stage of ATMP regulation, market access, and clinical use, cross-jurisdictional participation allowed for a more comprehensive understanding of real-world practices and may inform regional alignment of pharmacists’ roles in ATMP governance in the future.

Nevertheless, there are still several limitations. Firstly, the use of network-based recruitment introduced potential selection bias, resulting in a Delphi panel predominantly comprising pharmacists and pharmacy administrators. With limited representation from other key stakeholders such as physicians, bedside nurses, frontline pharmacists with hands-on experience in ATMPs delivery, and industry representatives, the findings may not fully capture the multidisciplinary perspectives required for comprehensive ATMP governance by hospital pharmacists. Importantly, the absence of physicians and nurses may bias the proposed role interfaces and inter-professional boundaries toward pharmacy-centric assumptions, potentially underrepresenting clinical workflow contingencies, escalation pathways, and day-to-day accountability arrangements that are negotiated in frontline practice. As such, the CF should be interpreted primarily as guidance for pharmacists’ competencies rather than a definitive delineation of inter-professional boundaries. Future studies would benefit from involving a wider range of multidisciplinary stakeholders to validate and refine the framework, particularly with respect to inter-professional roles and operational workflows in real-world ATMP practice.

Secondly, the CF is subject to potential cultural and institutional biases, as it was developed within Macau’s specific healthcare infrastructure and regulatory context. Furthermore, due to Macau’s limited local experience with ATMP use, certain domains (e.g. manufacturing, supply chain, and cross-border cold-chain logistics) were theoretically included but lack extensively validated in local practice. Future studies could empirically evaluate these domains via pilot implementation and process audits, simulation-based drills of cross-border logistics scenarios, and mixed-methods feedback from multidisciplinary staff to assess feasibility, usability, and workflow integration.

Thirdly, while offering evidence-informed competency standards, the CF’s acceptability, feasibility, reliability, and predictive validity require further investigation. Although the present study did not develop a scored measurement instrument, it provides a necessary foundation for future instrument development and validation. Future research should broader stakeholder input and conduct iterative assessments across diverse institutional settings to examine the CF across disciplines, mitigate biases, and explore its utility for formal credentialing or stratifying core versus extended competencies.

Conclusions

This study developed a consensus-based CF for hospital pharmacists managing ATMPs in an emerging-market setting, with Macao serving as the development and content-validation context. By integrating systematic evidence with expert consensus, the CF is expected to address existing institutional and practice gaps by providing structured guidance for the safe and effective use of ATMPs and fostering multidisciplinary collaboration in hospital settings. Although grounded in the Macao context, it offers a transferable reference for healthcare systems across the GBA and other emerging markets. Future research should further examine the CF’s feasibility, acceptability and impact across diverse institutional contexts, explore its integration into pharmacist training, credentialing, and performance evaluation systems, and ensure its continuous refinement in line with local practice, regulatory development, and evolving professional needs. Specifically, future study designs including multi-center cross-sectional surveys engaging broader multidisciplinary stakeholders to assess its generalizability, and prospective pre-post implementation studies to evaluate its real-world impact on clinical practice should be prioritized.

Abbreviations

ATMP

Advanced Therapy Medicinal Product

BTD

Breakthrough Therapy Designation

CAT

Committee for Advanced Therapies

AAV

Adeno-Associated Virus

ACCORD

ACcurate COnsensus Reporting Document

ACCP

American College Of Clinical Pharmacy

AFPC

Association Of Faculties Of Pharmacy Of Canada

ATMPs

Advanced Therapy Medicinal Products

BSL

Biosafety Levels

CAR-T

Chimeric Antigen Receptor T-Cell

CDE

Center For Drug Evaluation

CF

Competency Framework

CIs

Confidence Intervals

CoA

Certificates Of Analysis

CPD

Continuing Professional Development

CQI

Continuous Quality Improvement

Cr

Authority Coefficient

CRS

Cytokine Release Syndrome

DI

Disagreement Index

E&E

Evidence And Elaboration

GBA

Guangdong–Hong Kong–Macao Greater Bay Area

GbCF

Global Competency Framework

GMO

Genetically Modified Organism

GTMPs

Gene Therapy Medicinal Products

HCPs

Healthcare Professionals

ICANS

Immune Effector Cell-Associated Neurotoxicity Syndrome

IPR

Interpercentile Range

IPRAS

Symmetry-Adjusted Interpercentile Range

NMPA

National Medical Products Administration

POC

Point-Of-Care

QP

Qualified Person

RMPs

Risk Management Plans

SAR

Special Administrative Region

Authors' contributions

JS - conception, data collection, data analysis, draft and editing manuscript, HH- data collection, data analysis, editing manuscript. COLU - conception, data collection, data analysis, draft and editing manuscript, administration, funding acquisition. The authors confirm that we have substantially contributed to the conception and design of the research article and interpreting the relevant content of competency framework and have been involved in writing the research article and revising it for intellectual content.

Funding

This work was supported by a grant from University of Macau (MYRG-GRG2023-00087-ICMS, MYRG-GRG2024-00147-ICMS-UMDF, MYRG-CRG2024-00024-ICMS-IAS), Centre for Pharmaceutical Regulatory Sciences, University of Macau, Institute of Chinese Medical Sciences, University of Macau, and the Science and Technology Development Fund, Macau SAR (file no. 005/2023/SKL).

Data availability

The authors confirms that all data generated or analyzed during this study are included in this manuscript and supplementary information files.

Declarations

Ethics approval and consent to participant

Ethical approval number (HE-0132-2024) was obtained from the Sub-Panel on Social Science & Humanities Research Ethics (Human Participants), Research Ethics Panel on Research Committee of the University of Macau. Confidentiality was maintained. Informed consent by email was obtained from the Delphi experts. Published data were handled anonymously and used only for research. This study adhered to the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.