ICH Q7 explained: GMP for active pharmaceutical ingredients, chapter by chapter, with peptide APIs in focus

ICH Q7 is the document an API manufacturer is inspected against, whether the inspector comes from FDA, an EU member state or a PIC/S authority. It is also the most practical answer to the question “what does GMP mean for an API?”. This guide explains what ICH Q7 covers, where it starts to apply in a peptide synthesis, what each of its 20 chapters requires, what the 2015 Questions and Answers clarified, how inspectors use it, and how it compares with the US finished-product regulation, 21 CFR Part 211.

What is ICH Q7?

ICH Q7, “Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients”, was released for consultation at Step 2 on 19 July 2000 and adopted at Step 4 on 10 November 2000 [1]. It was first coded Q7A and recodified as Q7 in November 2005 [1]. Its objective is to provide guidance on GMP for the manufacture of APIs “under an appropriate system for managing quality” and to help ensure that APIs “meet the requirements for quality and purity that they purport or are represented to possess” [1].

Three features shape how it is read:

• “Should” means expected. In ICH Q7 “should” indicates “recommendations that are expected to apply unless shown to be inapplicable or replaced by an alternative demonstrated to provide at least an equivalent level of quality assurance” [1].
• It is not a filing guideline. It “is not intended to define registration/filing requirements or modify pharmacopoeial requirements”, although “all commitments in registration/filing documents must be met” [1].
• CGMP and GMP are the same here. “The terms ‘current good manufacturing practices’ and ‘good manufacturing practices’ are equivalent” [1].

Region	How ICH Q7 is implemented	Ref
United States	Published as final FDA guidance for industry (September 2016)	[2]
European Union	EudraLex Volume 4, Part II, which began as Annex 18 “reflecting the EU’s agreement to ICH Q7A”	[3], [4]
PIC/S participating authorities	PIC/S GMP Guide Part II, PE 009-18, dated 24 September 2026	[5]

What does ICH Q7 cover?

ICH Q7 “applies to the manufacture of APIs for use in human drug (medicinal) products” made “by chemical synthesis, extraction, cell culture/fermentation, by recovery from natural sources, or by any combination of these processes” [1]. For sterile APIs it applies “only up to the point immediately prior to the APIs being rendered sterile” [1]. It excludes vaccines, whole cells, whole blood and plasma, plasma derivatives and gene therapy APIs, and does not apply to medical gases, bulk-packaged drug products or radiopharmaceutical-specific aspects [1].

ICH Q7 defines an API as “any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product” [1]. Its definition of “manufacturing” is broad: “all operations of receipt of materials, production, packaging, repackaging, labelling, relabelling, quality control, release, storage and distribution of APIs and the related controls” [1]. Testing laboratories, packers and distributors are therefore in scope for the operations they perform.

For peptides, both main routes are covered. Synthetic peptides follow the chemical manufacturing pathway; recombinant peptides follow the biotechnology pathway, with section 18 adding controls for APIs “manufactured by cell culture or fermentation using natural or recombinant organisms” [1].

Where does GMP start for a peptide API?

ICH Q7 applies from the “API starting material”, defined as “a raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API” [1]. “The company should designate and document the rationale for the point at which production of the API begins”, and the guide “does not apply to steps prior to the introduction of the defined ‘API Starting Material’” [1]. The Q&A adds that “an appropriate level of controls suitable for the production of the API starting material should be applied” and that the starting material is “normally” defined in the regulatory filing and approved in review [6].

The justification itself belongs to ICH Q11, and ICH has confirmed that a Q11 “starting material” and a Q7 “API starting material” are “intended to refer to the same material” [7]. ICH Q11 notes that peptides synthesised on a solid support are a case where “there is a more limited relationship between risk and number of steps from the end of the manufacturing process” [8], which is why peptide starting materials sit close to the beginning of the route.

ICH Q7 Table 1 step (chemical manufacturing)	Peptide by SPPS	Peptide by fermentation (section 18)	Ref
Before the starting material	Synthesis of protected amino acid derivatives	Establishment of master and working cell banks	[1]
Introduction of starting material	Protected L-amino acid derivatives; resin preloaded with the first amino acid	Maintenance of the working cell bank	[1], [9]
Production of intermediates	Chain assembly; cleavage and deprotection to crude peptide	Cell culture and/or fermentation	[1], [9]
Isolation and purification	Preparative chromatography, fraction pooling, isolation (often lyophilisation)	Isolation and purification	[1], [9]
Physical processing and packaging	Packaging and labelling of the API	Packaging and labelling of the API	[1]

EMA’s synthetic peptide guideline says “protected natural L-amino acid derivatives… are generally acceptable as starting materials”, that “peptide synthesis resins preloaded with the first amino acid… are also considered starting materials”, and that “the unloaded solid support resin itself is not considered a starting material” [9]. Under ICH Q7, the stringency of GMP “should increase as the process proceeds from early API steps to final steps, purification, and packaging” [1].

ICH Q7 chapter by chapter

Chapter	What it requires (selected)	Peptide API note
1 Introduction	Objective, applicability, scope, Table 1	Defines where GMP starts [1]
2 Quality management	Quality unit “independent of production” with QA and QC responsibilities; main responsibilities “should not be delegated”; internal audits; annual product quality review [1]	Quality unit releases or rejects every API batch
3 Personnel	Qualified staff; training “should be periodically assessed”; hygiene; consultants [1]	SPPS and preparative HPLC operators trained for the specific operations
4 Buildings and facilities	Design, utilities, water, containment; dedicated areas for highly sensitising materials and consideration of them for high pharmacological activity [1]	Dedicated areas are to be considered for highly potent materials [1]
5 Process equipment	Design, maintenance, cleaning, calibration; “GMP related computerized systems should be validated” [1]	Synthesisers, chromatography skids and freeze-dryers are GMP equipment
6 Documentation and records	Specifications, master production instructions, batch production and laboratory records; retention for at least 1 year after expiry, or 3 years after complete distribution for APIs with retest dates [1]	Batch records must trace each sub-batch through pooling
7 Materials management	Supplier approval; “at least one test to verify the identity of each batch of material”; full analysis on at least three batches before reducing in-house testing [1]	Applies to protected amino acids, resins, reagents and solvents
8 Production and in-process controls	Written procedures to monitor steps that cause variability; time limits; blending; contamination control [1]	Coupling, deprotection and cleavage controls; fraction pooling criteria [9]
9 Packaging and labelling	Controls on packaging materials and labels; procedures to prevent mix-ups [1]	Peptides are often hygroscopic, which affects packaging and storage choices [9]
10 Storage and distribution	Release for distribution only after quality unit release [1]	Cold storage where the stability data require it
11 Laboratory controls	Testing of each batch; an impurity profile for each API; Certificates of Analysis; stability monitoring; retest dating; reserve samples [1]	Impurity profile by HPLC and LC-MS is central for peptides
12 Validation	Validation policy; qualification; prospective validation preferred; cleaning validation; analytical method validation [1]	Measures against cross-contamination when different peptides are purified on the same column [9]
13 Change control	Formal system; quality unit approval; notification of dosage form manufacturers of changes that can affect API quality [1]	Resin, coupling reagent or purification changes are typical changes
14 Rejection and re-use	Reprocessing, reworking, recovery of materials and solvents, returns [1]	Routine repurification of side fractions is part of the process, not reprocessing [9]
15 Complaints and recalls	Record and investigate all quality complaints; recall procedure [1]
16 Contract manufacturers	Contract manufacturers and laboratories follow ICH Q7; written agreement; audit rights; no subcontracting without approval [1]	Covers outsourced synthesis steps and contract testing
17 Agents, brokers, traders, distributors	Quality system; complete traceability to the original manufacturer; transfer of information [1]	A CoA should show the name and address of the original manufacturer [1]
18 Cell culture and fermentation	Cell bank maintenance, culture, harvest, purification, viral removal [1]	Applies to recombinant peptide APIs
19 APIs for clinical trials	Controls “consistent with the stage of development”; independent quality unit approves each batch [1]	Early-phase peptide supply
20 Glossary	Definitions of API, intermediate, critical, deviation and others [1]

The requirements that matter most for peptide APIs

The quality unit

“There should be a quality unit(s) that is independent of production and that fulfills both quality assurance (QA) and quality control (QC) responsibilities” [1]. Its responsibilities “should not be delegated” and start with “releasing or rejecting all APIs” [1]. The Q&A clarifies that ICH Q7 “does not prescribe specifically who performs testing”, because “quality control” refers to activities rather than organisational structure; what matters is that the quality unit is responsible for release [6].

Product quality review

Reviews “should normally be conducted and documented annually” and include critical results, failed batches, critical deviations, changes, stability, complaints and recalls, and the adequacy of corrective actions [1]. The Q&A says the period can be adjusted “based upon manufacturing and campaign duration with adequate justification”, that a review is expected even if no manufacturing occurred, and that trend analysis “is usually an important element” [6]. For peptide APIs made in campaigns, this question comes up often.

Impurity profile, Certificates of Analysis and stability

ICH Q7 says “an impurity profile describing the identified and unidentified impurities present in a typical batch produced by a specific controlled production process should normally be established for each API” [1]. Authentic Certificates of Analysis “should be issued for each batch of intermediate or API on request”, list each test “including the acceptance limits, and the numerical results obtained”, and be “dated and signed by authorised personnel of the quality unit(s)” [1]. Stability is monitored through “a documented, on-going testing program”, and “common practice is to use a retest date, not an expiration date” [1]. The thresholds a peptide impurity profile is judged against come from peptide-specific texts, covered in our impurities guide.

Validation

Process validation is “documented evidence that the process, operated within established parameters, can perform effectively and reproducibly”. “Prospective validation is the preferred approach” and should be completed “before the commercial distribution of the final drug product manufactured from that API” [1]. The Q&A states that ICH Q7 “does not preclude the lifecycle approach” [6], the continuous approach described in ICH Q10 [10]. Cleaning procedures “should normally be validated”, with validation directed at the steps where carryover “poses the greatest risk to API quality” [1].

Reprocessing and repurification

ICH Q7 treats repeating “a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the established manufacturing process” as generally acceptable reprocessing [1]. EMA’s peptide guideline goes further for chromatographic purification: “when routine repurification is carried out, this is not considered reprocessing but part of the regular manufacturing process and should be justified”, and likewise a routine repeat coupling “is not considered reprocessing” [9]. The terms reprocessing, recovery and rework “should be used and understood as defined in ICH Q7” [9].

Intermediates in SPPS

ICH Q7 defines an intermediate as “a material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API” [1]. EMA applies that definition to SPPS: “the end product of SPPS is the peptide bound to the resin”, which is an intermediate but “normally not subject for intermediate testing”, while “the crude peptide after cleavage and deprotection is typically considered to be an intermediate” with justified specifications [9].

What the ICH Q7 Q&A (2015) clarified

The Q&A document, approved on 10 June 2015, answers implementation questions section by section [6].

Question	Answer in brief	Ref
Should GMP apply before the API starting material?	No, but appropriate controls are expected; the starting material is normally defined in the filing	[6]
Does the quality unit have to perform release testing?	No; it is responsible for release and oversight, not necessarily for running the tests	[6]
How often is a product quality review needed?	Generally annually, adjustable with justification; still expected when nothing was made	[6]
Are on-site audits required to qualify suppliers?	No; a risk assessment can set the audit strategy	[6]
Is the lifecycle approach to process validation acceptable?	Yes	[6]
Can a parameter range be widened because of a deviation?	No, though investigation data can support additional studies	[6]
Does a change of starting material source need validation?	It should be assessed for impact; in most cases validation is expected for a different source unless otherwise justified	[6]
Who tells the drug product manufacturer about API changes?	Each party in the supply chain passes information to the next customer	[6]
Can one set of equipment make preclinical and clinical batches?	Yes, if operated under GMP with effective cleaning, safe residue limits and containment	[6]

How inspections use ICH Q7

FDA

FDA’s API inspection program, compliance program 7356.002F, was issued on 1 August 2025 with an implementation date of 2 September 2025, revised to add elements of ICH Q9(R1), Q10 and Q12 and the control of hazardous impurities [11]. It states that “ICH Q7 represents FDA’s current thinking on CGMP for APIs. Thus, API and related manufacturing and testing facilities that follow this guidance will generally be considered in compliance with the statutory CGMP requirement”, while “alternative approaches may be used” if they meet section 501(a)(2)(B) of the FD&C Act [11].

The program applies to “polypeptides consisting of up to 40 amino acids that are manufactured by chemical synthesis or fermentation”, alongside small molecules and fermented antibiotics; protein APIs are inspected under a different program [11]. It uses a systems-based approach with six systems: quality, facilities and equipment, materials, production, packaging and labelling, and laboratory control [11]. “An inspection under this program is defined as audit coverage of two or more systems, including mandatory coverage of the quality system” [11]. Inspections are either surveillance (routine) or for-cause, and a firm “is not in a sufficient state of control if any system is significantly noncompliant” [11].

For a US filing, FDA’s draft DMF guidance adds that DMFs for drug substances “should state that the material covered by the DMF is manufactured under current good manufacturing practices”, and points to ICH Q7 and Q11 for the definition and criteria for starting materials and intermediates [12].

EU and PIC/S

In the EU, Article 46(f) of Directive 2001/83/EC places on manufacturing authorisation holders the obligation “to use only active substances that have been manufactured in accordance with Good Manufacturing Practice for starting materials”, and Member States agreed that former Annex 18 “should form the basis of the detailed guidelines to create Part II of the GMP Guide” [3]. EudraLex Volume 4 publishes Part II alongside Part I (medicinal products) and the Annexes [4]. PIC/S publishes the same text as Part II of its GMP Guide [5].

ICH Q7 vs 21 CFR Part 211

21 CFR Part 211 contains “the minimum current good manufacturing practice for preparation of drug products… for administration to humans or animals” [13]. Under 21 CFR 210.1, failure to comply with Parts 210 and 211 renders a drug adulterated under section 501(a)(2)(B) [14]. An API is not a drug product, so FDA applies the statutory CGMP requirement to APIs and uses ICH Q7 as its current thinking [11].

Topic	ICH Q7 (APIs)	21 CFR Part 211 (finished drug products)	Ref
Legal form	Harmonised guidance (“should”)	Binding regulation (“shall”)	[1], [13]
Scope	APIs, from the API starting material	Drug products	[1], [13]
Quality organisation	Quality unit(s) independent of production, with QA and QC duties	Quality control unit with authority to approve or reject components and drug products	[1], [13]
Batch record retention	At least 1 year after expiry; at least 3 years after complete distribution for APIs with retest dates	At least 1 year after the expiration date of the batch (3 years after distribution for certain exempt OTC products)	[1], [13]
Dating	Retest date common practice	Expiration date determined by stability testing	[1], [13]
Clinical-trial material	Section 19 with phase-appropriate controls	Phase 1 investigational drugs exempt from Part 211 under 21 CFR 210.2(c), but statutory CGMP still applies	[1], [14], [15]

The concepts are shared: an independent quality function, written procedures, contemporaneous records, investigation of deviations, change control and validated methods. The differences reflect what is being made. An API is usually a bulk powder with a retest date that may be stored and shipped to several drug product manufacturers; a drug product is the final dosage form with an expiry date.

ICH Q7 vs EU GMP Part II

EU Part II follows the ICH Q7 chapter structure but is not identical. It adds a section 2.2 on quality risk management, defined as “a systematic process for the assessment, control, communication and review of risks to the quality of the active substance”, and states that the level of effort, formality and documentation “is commensurate with the level of risk” [3]. In ICH Q7, section 2.2 is the responsibilities of the quality unit [1]. The PIC/S Part II also carries a section 2.2 on quality risk management [5]. The 2014 revision of Part II also clarified the relationship between its section 17 and EU good distribution practice for active substances [3].

How Winhycare Pharma supplies peptide APIs

Winhycare Pharma supplies semaglutide, tirzepatide, retatrutide, cagrilintide and BPC-157 as APIs to licensed manufacturers; see peptide APIs. For semaglutide we support US-DMF Type II dossiers and CTD Module 3 CMC documentation for customers’ own filings. Our research peptides are a separate, research-use-only range at purity of ≥99% as stated in our product brochure, and custom peptide synthesis is available. For API enquiries, including audit and documentation requests: enquire about semaglutide API or request research peptides.

For laboratory research use only. Not for human or veterinary use.