Friday, 23 March 2012

GRASE, Grandfathered and DESI Drugs

GRASE Drugs-
  • The abbreviation of the term GRASE is -Generally Recognized as Safe and Effective
  • GRASE Drugs are certain old drugs that do not require prior approval from FDA in order to be marketed because they are generally recognized as safe and effective based on published scientific literature.
  • It is not an easy standard for a drug to qualify as GRASE. For a drug to qualify under the category of GRASE, it has to fulfill the following criteria-
  1. The Drug must have been subjected to adequate and well controlled clinical investigations that established its safety and effective.
  2. The Investigation results must be published in the scientific literature so that they are available to qualified experts.
  3. Experts must generally agree, based on those published studies, that the drug is safe and effective for its intended uses.
  • A product's general recognition as safe and effective must be demonstrated by at least the same quality and quantity of data necessary to support FDA approval for marketing.
  • It is unlikely that any currently marketed prescription drug is GRASE.
Note: The term GRAS (Generally Recognized as Safe) was used in 1938, Federal Food, Drug, and Cosmetic act.
The term GRASE (Generally Recognized as Safe and Effective) was used in 1962 amendment to the   Federal Food, Drug, and Cosmetic act.

Grandfathered Drugs
  • Drugs that entered the market before the passage of the 1938 act or the 1962 amendments to the act are often referred to as grandfathered drugs.
  • Under the 1962 grandfather clause, the FFDCA exempts a drug from the effectiveness requirements if its composition and labeling have not changed since 1962 and if, on the day before the 1962 amendments became effective, it was
  1.  Used or sold commercially in the United States
  2.   Not a new drug as defined by the act at that time
  3.   Not covered by an effective application
  • Many older drugs without FDA approval claim to be grandfathered; however, FDA believes that very few drugs are on the market that are actually entitled to grandfather status because the drugs currently on the market likely differ from the previous versions in some respect, such as formulation, dosage or strength, dosage form, route of administration, indications, labeling, or intended patient population.
DESI Drugs- 
  • The abbreviation of term DESI is- Drug Efficacy Study Implementation
  • Drugs that entered the US market between 1938 and 1962 and that were approved for safety but not effectiveness are referred to as DESI drugs.. Drugs that are IRS (Identical related or Similar )  to such drugs are also called DESI drugs.
  • “Safety” was the criteria for the approval of New Drugs between the passage of 1938, Federal Food, Drug, and Cosmetic act and its amendment in 1962 ( Kefauver-Harris amendment).
  • “Safety and Efficacy criteria“had to be met as per the Kefauver-Harris amendment for the approval of New Drugs.       
  • The Kefauver-Harris amendment also required that FDA evaluate the safety and the effectiveness of new drugs marketed between 1938 and 1962.
  • Drug Efficacy Study Implementation (DESI) was a program begun by the Food and Drug Administration (FDA) after the requirement by Kefauver-Harris amendment that all drugs marketed between 1938 and 1962 be safe and effective.
  • The DESI program was intended to classify all pre-1962 drugs that were already on the market as either effective, ineffective, or needing further study.
  • The Drug Efficacy Study Implementation (DESI) evaluated over 3000 separate products and over 16,000 therapeutic claims.
  • By 1984, final action had been completed on 3,443 products; of these, 2,225 were found to be effective, 1,051 were found not effective, and 167 were pending.
Keywords- Federal Food, Drug and Cosmetic act (FFDCA)-1938, Kefauver-Harris amendment-1962. 


Thursday, 8 March 2012


What is the Full form of abbreviation, CEP?
Certificate of Suitability to the monographs of the European Pharmacopoeia (or) Certificate of suitability of monographs of the European Pharmacopoeia (or) Certification of suitability of European Pharmacopoeia monographs
It is also informally referred to as Certificate of Suitability (COS)

What is a CEP?
It is the certificate which is issued by Certification of Substances Division of European Directorate for the Quality of Medicines (EDQM), when the manufacturer of a substance provides proof that the quality of the substance is suitably controlled by the relevant monographs of the European Pharmacopoeia.

For which substances, applications for the grant of CEPs can be submitted?
Applications for the grant of CEPs can be submitted to EDQM if monograph (general monograph and/or specific monograph) has been adopted by the European Pharmacopoeia for the following-
  • Organic or inorganic substances (active or excipients), manufactured or extracted.
  • Sterile Active Substances
  • Substances produced by fermentation as indirect gene products, which are metabolites of microorganisms, irrespective of whether or not the microorganisms have been modified by traditional procedures or r-DNA technology
  • Products with risk of transmitting agents of animal spongiform encephalopathies (TSE)
  • Herbal Drugs and Herbal Drug Preparations
For which substances CEP is not granted?
  • Direct gene products (proteins)
  • Products obtained from human tissues
  • Vaccines
  • Blood products and preparations.
What are the Legislations which describe certification Procedure?
Directives 2001/82/EC and 2001/83/EC, as amended, of the European Council and of the Parliament.
Guidelines to be referred for preparing Dossier to obtain a CEP 
Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 04 1 4R)
Application form and template for QOS 
Link for Downloading Application form and template of QOS.
Note: Click on the hyperlinks in blue for application form and template of QOS to download them.
Online Database of Approved CEPs 
Link to Online Databases of Approved CEPs 
Registration Fees  
Registration fees for various New CEP Applications 

 Link to top 10 deficiencies in New Applications for grant of CEPs 

Recognition of CEPs- CEPs are recognised by all the member countries of the European Union and also   other Countries like Canada, Australia, New Zealand, Tunisia and Morocco. 
Advantages of CEPs-
  •  It is valid for 5 Years.
  • An API manufacturer need not file an ASMF/EDMF in all the member countries involved in DCP/MRP Procedures if the manufacturer has obtained CEP for that specific API. Sending a Copy of CEP will do.
  • Centralised evaluation of Dossier by only one agency i.e EDQM.
Keywords: CEP, EDQM,  Resolution AP-CSP (07) 1, Directives 2001/82/EC and 2001/83/EC.