In summary, FDA's guidance for industry, premised on ICH Q11, provides a blueprint for drug-substance manufacturers to follow
when preparing a submission as part of the drug- substance application process, regardless whether a traditional or enhanced
approach to design and development is pursued. It is imperative that subsidiary ICH and FDA guidance documents be reviewed
and understood as these documents provide relevant information required as part of the drug-substance submission process.
Fundamental requirements needing to be described, in sufficient detail, in support of the submission process are design and
development, manufacturing processes, control strategy, use of starting materials, CQAs, approach to QRM, design space, and
approach to continuous improvement. In closing, the CTD format has become the prescribed submission format for regulatory
authorities. Ensuring that all of the technical data (i.e., quality, safety, and efficacy) required by the CTD format is organized
by specific module will hopefully facilitate an orderly and efficient review of the drug substance application by the appropriate
1. FDA, Guidance for Industry: Q11 Development And Manufacture Of Drug Substances (FDA, November 2012).
2. ICH, Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/biological Entities) (May 2012).
3. ICH, ICH Website homepage,
http://www.ich.org/, accessed January 12, 2013.
4. ICH, Q8 (R2) Pharmaceutical Development (ICH, August 2009).
5. FDA, Guidance for Industry: Q7A Good Manufacturing Guidance For Active Pharmaceutical Ingredients (FDA, August 2001).
6. ICH, Q5A (R1) Chemical Synthesis and Elements of Biological Origin (ICH, September 1999).
7. ICH, Q5B Quality Of Biotechnological Products: Analysis Of The Expression Construct In Cells Used For Production of R-DNA Derived
Protein Products (ICH, November 1995).
8. ICH, Q5C Quality of Biotechnological Products: Stability Testing Of Biotechnological/Biological Products (ICH, November 1995).
9. ICH, Q5D Derivation and Characterization of Cell Substrates Used for Production Of Biotechnological/Biological Products (ICH, July 1997).
10. ICH, Q5E Compatibility Of Biotechnological/Biological Products Subject To Changes In Their Manufacturing Process (ICH, November 2004).
11. FDA, Draft—Guidance For Industry: Providing Regulatory Submissions In Electronic Format—Certain Human Pharmaceutical Product
Applications And Related Submissions Using the eCTD Specifications (FDA, January 2013).
12. FDA, Guidance for industry: M4Q: CTD–Quality (FDA, August 2001).
13. ICH, M4 (R3) Organization Of The Common Technical Document For The Registration Of Pharmaceuticals For Human Use (ICH, January 2004).
14. ICH, M4E (R1) The
Common Technical Document For The Registration Of Pharmaceuticals For Human Use: Efficacy (ICH, September 2002).
15. ICH, M4Q (R1) The Common Technical Document For The Registration Of Pharmaceuticals For Human Use: Quality (ICH, September 2002).
16. ICH, M4S (R2) The
Common Technical Document For The Registration Of Pharmaceuticals For Human Use: Safety (ICH, December 2002). PT
Bob Mehta is a principal consultant and recruiter at
http://www.gmpisoexpert.com/ and provides consulting service in pharma, biotech, medical device, API, and food/dietary supplement industries, firstname.lastname@example.org
Submitted: Dec. 28, 2012. Accepted: January 24, 2013.