Dear Dr. Adola,

Please submit your revised manuscript by Jan 02 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Maher Darwish

Academic Editor

PLOS ONE

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Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #1: This is a cross-sectional, facility-level assessment of cGMP implementation in six large-scale Ethiopian pharmaceutical manufacturers. The authors used a WHO-based checklist (S2) and scored sub-elements (FC=3, PC=2, NC=1) to produce company compliance percentages and identify weak areas (QA, QRM, HVAC, documentation, internal audit, complaint/recall). Strengthening local manufacturing quality systems is high priority worldwide; the paper addresses an important regulatory and public-health issue. Comparable regional analyses exist and make this work useful for national stakeholders.

However, few concerns have been raised for this paper. First, selection of only 6 companies, the sampling strategy risks selection bias, the manuscript does not describe how companies were recruited or whether non-participation occurred (response rate among 10 approached). This affects possible non-response bias, although I understand that companies might not be very cooperative sometimes. Second, The numerical conversion (FC=3, PC=2, NC=1) and the derived % thresholds ( >85%=high, 80–85%=medium, <80%=low) are not justified/validated. No sensitivity analysis or inter-rater reliability reported to show reproducibility between the two pharmacist assessors. Third, only 5 personnel per company (N=30) were interviewed, with such small cell counts the meaningfulness of some p-values is questionable and should be reported with caution. Fourth, no multivariable analysis to control confounding (e.g., company age, number of lines, certification status). Fifth, regarding data availability, authors claim “All relevant data are within the manuscript and Supporting Information” but raw checklists / per-company itemized scores are absent. For reproducibility, provide de-identified item-level datasets or an aggregated CSV in a public repository.

I recommend the authors to explain how the 6 companies were chosen from the 10 approached and discuss representativeness relative to the 12 large manufacturers in Ethiopia in a more detailed manner. Also, I advise the authors to report inter-rater reliability (Cohen’s kappa or % agreement) between the two pharmacists who collected/check-listed data. Provide the full checklist scoring rubric in the supplement (item-level scores per company, de-identified). Please add a methods paragraph justifying FC/PC/NC numeric mapping, explain why thresholds (>85%, 80–85%, <80%) were chosen (cite similar validation if available), or present sensitivity analyses showing how results shift with alternative cutoffs. Discuss selection bias, small sample size, potential Hawthorne effect (sites may temporarily improve practice during audit), lack of PAT adoption measurement detail, and language/translation limitations if any.

With the methodological clarifications and stronger transparency (itemized data, reliability stats) requested above, the manuscript could be acceptable.

Reviewer #2: Review Document

Title of Manuscript:

Assessment of Current Good Manufacturing Practice (cGMP) Compliance in Pharmaceutical Manufacturers in Ethiopia: A Cross-sectional Descriptive Study

General Comments

The topic is relevant and timely, addressing an important issue for pharmaceutical quality systems in developing countries. However, the manuscript requires significant revision to improve clarity, scientific rigor, consistency, and alignment between citations, text, and methodology.

Specific Comments

1. Title

• The title is clear and informative.

2. Background

• The background provides a good overview; however, there is a major issue with the use of references.

o For example, in paragraph 5, you wrote:

"Historically, most Ethiopian pharmaceutical manufacturers have produced drugs that do not meet GMP standards..."

However, the cited reference actually discusses the historical development of pharmaceutical manufacturing in Ethiopia (e.g., establishment of the first company in 1964, post-1991 expansion, and policy adjustments), not noncompliance with GMP or patient harm.

➤ Action: Review and replace or remove mismatched citations throughout the background section.

• The background should also clearly state the existing research gap or problem that motivated this study.

• To assess cGMP compliance, the background must include the criteria or operational definition used to evaluate “degree of compliance.”

• In the objective section, ensure consistency in terminology — the manuscript alternates between “to evaluate” and “to assess.” Choose one and use it consistently throughout.

3. Methods

• The data collection methods should be presented more clearly and concisely. Avoid repetition.

o You mentioned both:

� “Data was collected from key technical and managerial personnel directly involved in implementing product quality assurance systems…”

� “A standardized checklist based on national and international GMP standards was developed and employed…”

These statements overlap. Combine and clarify.

• The checklist used should have a proper reference (national/international GMP source).

• The inclusion and exclusion criteria need correction. You stated that small-scale pharmaceutical manufacturers were excluded — however, by definition, pharmaceutical industries are generally large-scale operations. Please revise this point for accuracy.

• Clarify what you mean by “high number of product batches” or “wide range of dosage forms.” Provide scientific or numerical justification for these terms.

• The statement that “five key personnel were purposively chosen from each company” requires justification. Why five? Was this number based on pilot testing, organizational structure, or literature precedent?

• Overall, the Methods section should be rewritten to:

o Remove unnecessary repetitions

o Improve logical flow

o Provide scientific rationale for sampling, inclusion/exclusion criteria, and data collection tools.

4. Results

• You reported that “Of the six participating companies, four are GMP certified.”

➤ Clarify whether the two uncertified companies are actually producing pharmaceuticals without certification. This is a serious issue and needs confirmation and contextual explanation.

• The compliance rating scale (“Not Compliant,” “Partially Compliant,” “Fully Compliant”) should be operationalized — specify the criteria or scoring system used to classify each category.

• The statement “Data was collected through interviews with key personnel from six companies” belongs in the Methods section — please remove or paraphrase it in the Results.

• When stating that “Most companies demonstrated a good level of compliance, though deficiencies ranged from minor to critical,” please define what constitutes minor and critical deficiencies.

5. Discussion

• The discussion compares the findings to studies conducted in large-scale industries, which may not be directly comparable to your context of six local companies.

➤ Reframe comparisons using studies with similar scale and methodology for more meaningful interpretation.

• Deepen the discussion by interpreting what the findings imply for regulatory oversight, capacity building, and industry practices in Ethiopia.

6. Conclusion

• The conclusion currently reads like a summary of results.

➤ It should instead highlight the key implications of the findings, potential policy or regulatory recommendations, and suggestions for future research.

7. References

• Ensure uniformity in reference formatting according to PLOS ONE style:

o Use et al. consistently.

o Include DOIs for published articles and URLs for non-published sources.

o Ensure consistency in placement of publication year (either after the author or at the end — not mixed).

o Italicize journal names.

• For example, reference #18 places the year differently — revise for consistency across all entries.

Overall Recommendation

The manuscript addresses an important national issue, but substantial revisions are required before it can be considered for publication. The authors should particularly focus on:

• Correcting mismatched citations in the background,

• Clarifying and justifying methodological choices,

• Defining compliance rating criteria, and

• Enhancing the clarity and consistency of references and conclusions.

Reviewer #3: Review – I can recommend publishing but there are some gaps that need to be addressed.

1. The manuscript's purpose is unclear; clarify why readers need to know about cGMP compliance in Ethiopia.

2. Does cGMP non-compliance affect international medicine exports from Ethiopia? Is there a broader impact?

3. Identify the Ethiopian regulatory authority responsible for enforcing WHO GMP compliance.

4. State the penalties for non-compliance in Ethiopia.

5. Define EFDA (Ethiopian FDA) and include it in the abbreviations section.

Reviewer #4: There are multiple grammatical errors in the text. Abbreviations should not be used for the first time in the abstract. There is no realistic conclusion based on the results obtained. The value of the research lies in providing a report to pharmaceutical manufacturers to implement GMP-based reforms, and the article does not mention a specific purpose for publication.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Attachments

Attachment

Submitted filename: Reviewer comments.docx

Dear Dr. Adola,

plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Maher Darwish

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

1. The manuscript's purpose is unclear; clarify why readers need to know about cGMP compliance in Ethiopia.

2. Does cGMP non-compliance affect international medicine exports from Ethiopia? Is there a broader impact?

3. Identify the Ethiopian regulatory authority responsible for enforcing WHO GMP compliance.

4. State the penalties for non-compliance in Ethiopia.

5. Define EFDA (Ethiopian FDA) and include it in the abbreviations section.</samp>

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #3: Yes

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Reviewer #1: (No Response)

Reviewer #3: The author has not provided a response to my initial questions. I would request the authors to kindly review the inital comments in detail, and provide a response to each question. I am attaching my questions again.

1. The manuscript's purpose is unclear; clarify why readers need to know about cGMP compliance in Ethiopia.

2. Does cGMP non-compliance affect international medicine exports from Ethiopia? Is there a broader impact?

3. Identify the Ethiopian regulatory authority responsible for enforcing WHO GMP compliance.

4. State the penalties for non-compliance in Ethiopia.

5. Define EFDA (Ethiopian FDA) and include it in the abbreviations section.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Assessment of current good manufacturing practice (cGMP) compliance in pharmaceutical manufacturers in Ethiopia: Cross-sectional descriptive study

PONE-D-25-40492R2

Dear Dr. Adola,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Maher Darwish

Academic Editor

PLOS One

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

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Reviewer #3: All comments have been answered, I have no further questions. I can now recommend publishing. Thank you.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #3: No

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