Pharmaceutical Regulatory Guideline

1. Reference Guidance

Process Validation

• Reference guideline/method:
  a. PV FDA JAN-2011
  b. EMA 2012 (including ICH Q8, Q10)

Blend Uniformity & Content Uniformity (stratified sampling)

• Reference guideline/method:
  a. ISPE (December 2014)
  b. ASTM E 2709/E2810
  c. USP Chapter No: 905

Friability

• Reference guideline/method:
  a. USP chapter 1216

Disintegration

• Reference guideline/method:
  a. USP chapter 709

Hold Time Study

• Reference guideline/method:
  a. World Health Organization; 2015: Annex 3 (WHO Technical Report Series, No. 992).

Dissolution

• Reference guideline/method:
  a. USP chapter 711

Cleaning Validation

• Reference guideline/method:
  a. ICH Q3 C (R5)
  b. Health Canada – Draft Cleaning Validation Guideline (GUI0028)
  c. FDA Guideline to Inspections Validation of Cleaning Process (1993)
  d. PICS, APIC
  e. HSA JAN 2013
  f. WHO Technical Series 937, 2006 Annex 4, Appendix 3

AQL (Critical-0.010% & non-critical-0.65%)

• Reference guideline/method:
  a. ISO 2859-1 General Inspection Level-III
  b. British Standard BS. 6001:1999-1 Level III

PSD Test for QC

• Reference guideline/method:
  a. GTP no.– GTP/USP/016

BD Test for QC

• Reference guideline/method:
  a. GTP no.– GTP/USP/017, /028

Stability

• Reference guideline/method:
  a. ICH-Q1A R2 to Q1E

MHRA/USFDA - PQR/APQR

• Reference guideline/method:
  a. EudraLex Volume 4
  b. Health Science Authorities (HSA)
  c. PICS

Transport Route Profiling & Qualification

• Reference guideline/method:
  a. WHO Stand-TRS 961 Annex 9

Quality Risk Management

• Reference guideline/method:
  a. ICH Q9
  b. WHO Guidelines-TRS-981, Annexure-II

2. ICH Guidance

ICH (International Council on Harmonization) Guidance:

• 1989-WHO Conference of Drug Regulatory Authorities produced action plans for the regulation of medical research (US, Japan, Switzerland, Canada, Europe)

1. Q1 Stability
2. Q2 Analytical Method Validation
3. Q3 Impurities
4. Q4 Recommendation of Pharmacopeia
5. Q5 Biotechnological Products
6. Q6 Specification Test Procedure and Acceptance Criteria
7. Q7 Good Manufacturing Practice (API)
8. Q8 Pharmaceutical Development
9. Q9 Quality Risk Management
10. Q10 Pharmaceutical Quality System
11. Q11 Development and Manufacture of Drug Substances
12. Q12 Life Cycle Management
13. Q13 Continual Manufacturing

3. ICH Stability Zones

4. Long-term Testing Conditions

5. Accelerated and Intermediate Testing Conditions

6. Stability Zone:

7. Product Approval Period (Approximately)

1. US – ANDA - FDA - 18 months to 24 months
2. EU – CTD - EU - 1 year to 2 years
3. South Africa - MCC - 8 months to 1 year (EDL)
4. Australia - CTD - TGA - 1 year to 2 years
5. New Zealand - CTD - MedSafe - 1 year to 2 years
6. Taiwan - MOH, Taipei - 1 year
7. Mexico - MOH - 1 year
8. Brazil – Similar - ANVISA - 9 months to 12 months

·        Generic - 6 months to 9 months

8. Regulatory Updates and Websites

1. DCGI (India): https://cdsco.gov.in
2. WHO: www.who.int
3. ICH: https://www.ich.org/
4. PICs: https://picscheme.org/
5. USFDA: https://www.fda.gov/drugs
6. Health Canada (Canada): https://www.canada.ca
7. MHRA (UK): https://www.gov.uk/government
8. EMEA (Europe): https://www.ema.europa.eu
9. EDQM (Europe): https://www.edqm.eu/en/
10. MCC (South Africa): https://www.mccza.com
11. TGA (Australia): https://www.tga.gov
12. ANVISA (Brazil): https://antigo.anvisa.gov.

9. Full Forms

• ISPE: International Society of Pharmaceutical Engineering
• ASTM: American Standards of Testing and Material
• ICH: International Council on Harmonization
• EMA: European Medicines Agency
• HSA: Health Science Authority
• SCM: Supply Chain Management
• RMG: Rapid Mixer Granulator
• SMG: Sizer Mixer Granulator
• RLAF: Reverse Laminar Air Flow
• LAF: Laminar Air Flow
• VTS: Vacuum Transfer System
• HVAC: Heating, Ventilation, and Air Conditioning
• AHU: Air Handling Unit
• HEPA: High Efficiency Particulate Air Filter
• ULPA: Ultra-Low Penetration Air
• VMP: Validation Master Plan
• LOAEL: Lowest Observed Adverse Effect Level
• NOEL: No Observable Effect Level
• PDE: Permitted Daily Exposure
• ADI: Acceptable Daily Intake
• MAR: Maximum Allowable Residue
• MACO: Maximum Allowable Carryover
• PIC/S: Pharmaceutical Inspection Co-operation Scheme
• CTD: Common Technical Document
• MSDS: Material Safety Data Sheet
• BOPP: Biaxial Oriented Polypropylene
• MPD: Master Packing Documents
• CPV: Continuous Process Validation
• CPP: Critical Process Parameters
• CQA: Critical Quality Attribute
• SUPAC: Scale-Up and Post Approval Changes
• SUPAC IR: Immediate Release
• SUPAC MR: Modified Release

10. Certification and Standards of ISO

1. ISO 9001:2015 - Quality Management System
2. ISO 14001:2015 - Environmental Management System
3. ISO 45001:2018 - Occupational Health & Safety Management System
4. ISO 13485 - Medical Device

11. 21 CFR Part 211 (Subparts & Clauses)

1. Personnel & Qualifications

·        Clause:
211.25 Personnel Qualifications.
211.28 Personnel Responsibilities.

2. Building & Facilities

·        Clause:
211.42 Design and Construction Features.
211.44 Lighting.
211.46 Ventilation, Air Filtration, Air Heating, and Cooling.
211.48 Plumbing.
211.50 Sewage and Refuse.
211.52 Washing and Toilet Facilities.
211.56 Sanitation.
211.58 Maintenance.

3. Equipment

·        Clause:
211.63 Equipment Design, Size, and Location.
211.65 Equipment Construction.
211.67 Equipment Cleaning and Maintenance.

4. Drug Product Containers & Closures

·        Clause:
211.80 General Requirements.
211.82 Receipt and Storage of Untested Components, Drug Product Containers, and Closures.
211.84 Testing and Approval or Rejection of Components, Drug Product Containers, and Closures.
211.86 Use of Approved Components, Drug Product Containers, and Closures.
211.87 Retesting of Approved Components, Drug Product Containers, and Closures.
211.89 Rejected Components, Drug Product Containers, and Closures.
211.94 Drug Product Containers and Closures.

5. Production & Process Control

·        Clause:
211.100 Written Procedures; Deviations.
211.101 Charge-in of Components.
211.103 Calculation of Yield.
211.105 Equipment Identification.
211.110 Sampling and Testing of In-Process Materials and Drug Products.
211.111 Time Limitations on Production.
211.113 Control of Microbiological Contamination.
211.115 Reprocessing.

6. Packaging & Labelling Control

·        Clause:
211.125 Labelling Issuance.
211.130 Packaging and Labelling Operations.
211.134 Drug Product Inspection.
211.137 Expiration Dating.