The World Health Organization (WHO) issued guidelines (aligned with ICH Q7) to ensure
APIs are consistently produced and controlled according to quality standards. Below are
structured detailed notes for your reference:
WHO Good Manufacturing Practices
(GMP) for APIs – Detailed Notes
1. Introduction
APIs are the active substances used in drug formulations.
WHO GMP for APIs ensures safety, efficacy, and quality across the entire supply
chain.
Guidelines are harmonized with ICH Q7, EU GMP Part II, and PIC/S standards.
Scope:
o Covers manufacture, processing, packaging, storage, and distribution of
APIs.
o Includes starting materials, intermediates, and final APIs.
o Applies to both chemical and biological APIs (fermentation, biotech, plant,
animal origin).
2. Quality Management
API manufacturer must have a Pharmaceutical Quality System (PQS).
Senior management responsibility for quality.
Key elements:
o Quality manual, policies, SOPs.
o Documented quality unit (independent from production).
o Self-inspections and internal audits.
o Corrective and preventive actions (CAPA).
o Change management system.
3. Personnel
Adequate qualified staff with roles/responsibilities defined.
Training in GMP principles and job-specific duties.
Health and hygiene requirements (no infectious or communicable disease risk).
Access restricted to authorized personnel.
Visitors and contractors must be controlled.
4. Buildings and Facilities
Must be located, designed, and maintained to minimize risks of contamination, mix-
ups, and errors.
Segregation required for highly sensitizing, toxic, or biological materials.
Adequate ventilation, lighting, and environmental controls.
Controlled utilities (water, gases, air, steam).
Storage areas with temperature, humidity monitoring.
5. Process Equipment
Equipment must be designed, cleaned, maintained, and calibrated.
Cleaning validation required to prevent cross-contamination.
Dedicated equipment may be required for hazardous APIs (e.g., penicillins).
Computerized systems must comply with data integrity requirements (ALCOA+).
6. Documentation & Records
All manufacturing and quality activities must be documented.
Types of documents:
o Master production instructions.
o Batch production records (BPR).
o Analytical methods and results.
o Logbooks (equipment, calibration, cleaning).
Records must be legible, indelible, traceable.
Retention period: at least 1 year after expiry of API batch.
7. Materials Management
Starting materials, reagents, solvents, packaging materials must be:
o Approved suppliers.
o Qualified before use (identity testing mandatory).
Quarantine system: separate status (approved, rejected, under test).
Proper storage conditions maintained.
Recycled solvents and reagents controlled and validated.
8. Production & In-Process Controls
Production must follow approved written procedures.
Critical process steps identified and validated.
In-process sampling and testing required.
Prevent cross-contamination by segregation, cleaning, and controls.
APIs must meet pre-defined specifications before release.
9. Packaging & Labelling
API packaging must protect against contamination and degradation.
Labels must include:
o API name, batch number, manufacturer.
o Retest date / Expiry date.
o Storage conditions.
Tamper-evident and secure packaging required for transport.
10. Storage & Distribution
Storage under controlled conditions (temperature, humidity).
First-In-First-Out (FIFO) / First-Expire-First-Out (FEFO) system.
Distribution records must ensure traceability.
APIs transported under conditions that maintain quality (e.g., cold chain).
11. Laboratory Controls
QC laboratories must be independent from production.
Methods validated for accuracy, precision, specificity, linearity.
Reference standards qualified and traceable.
Stability testing programs for APIs (as per ICH Q1).
Out-of-Specification (OOS) results must be investigated.
12. Validation
Process validation: Demonstrates consistent performance.
Cleaning validation: Prevents contamination.
Analytical method validation: As per ICH Q2.
Computerized system validation: Data integrity assurance.
Revalidation when significant changes occur.
13. Change Control
Formal system for reviewing and approving changes in:
o Process, equipment, facility, analytical methods, suppliers.
Risk-based evaluation required.
Documented approval and implementation.
14. Rejection & Reprocessing
Clear procedures for handling deviations, non-conformances, rejected materials.
Reprocessing allowed if scientifically justified and approved by quality unit.
Reworking must be exceptional, validated, and documented.
15. Complaints & Recalls
Documented procedures for handling product complaints.
Complaints must be investigated thoroughly.
APIs must be recallable from distribution chain.
Recall system must be rapid and effective.
16. Contract Manufacturing & Outsourcing
Written contract/agreement between contract giver and acceptor.
Responsibilities for GMP compliance clearly defined.
Contract facilities must be audited and qualified.
17. APIs for Clinical Trials
Must be manufactured under GMP principles.
Documentation and controls may be less extensive, but traceability and safety are
mandatory.
18. Self-Inspection & Audits
Internal self-inspections to monitor compliance.
Supplier audits (raw materials, intermediates, contract manufacturers).
Regulatory inspections may occur at any time.
✅ Summary: WHO GMP for APIs ensures that active substances are manufactured under
controlled conditions with robust quality systems, trained personnel, validated processes, and
proper documentation. It aligns with ICH Q7 and provides the backbone of API quality
assurance worldwide.
