Review Article A REVIEW ON LATEST GUIDELINES ON PROCESS VALIDATION OF EUROPEAN MEDICINES AGENCY KOTHA ARUN KUMAR*, N. VISHAL GUPTA, U NITIN KASHYAP, VEMURI PAVAN KUMAR Pharmaceutical Quality Assurance Group, Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Sri Shivarathreeshwara Nagara, Mysore-570015, Karnataka, India. Email: arunpharmaqa@gmail.com Received: 18 Jan 2014, Revised and Accepted: 01 Mar 2014 ABSTRACT Validation is an act of proving and documenting that a process functions efficiently. Process validation can be well-defined as documented proof that the process functions within established restrictions, can execute effectively and reproducibly to produce a pharmaceutical product meeting its determined conditions and quality features. The former note for guidance on process validation (1 March, 2001) of European Medicines Agency (EMA) emphasizes on traditional process validation. It describes the relationship between development studies and process validation data, connection between method of manufacture and process validation data, relationship between process validation and specification of the finished product. The latest draft of guidelines on process validation (29 march 2012) by EMA, is prepared based on the guidelines of ICH Q8, Q9, and Q10. It describes the utility of continuous process verification principles to replace traditional process verification. Continuous process verification (CPV) has been presented to cover a substitute method to process validation centered on a continuous monitoring of manufacturing process. It is intended to apply to medicinal products for human and veterinary use. The document provides guidance on the information to be considered for dossier submission and as such is mainly aimed at industry and assessors. Keywords: Critical process parameters, Critical quality attributes, Continued process verification, Continuous process verification, Process validation, Traditional process verification. INTRODUCTION Process validation is defined as an act of creating a written evidence or proof regarding the ability of a process to produce a product which meeting its critical quality attributes.[1] The present article is a compilation of different guiding principles on process validation by European medicines agency. Based on the guiding principles on process validation by EMA, the approaches for process validations are as follows: 1. Traditional process validation 2. Continuous process verification 3. Hybrid approach 4. Continued process verification 1. TRADITIONALPROCESS VALIDATION Process Validation documents should be created for all products to establish the capability of the manufacturing procedure at each onesite of production. It is recognized that, at the stage of market authorization proposal, process validation records may not always be available. However it is necessary that effective manufacturing procedures are continuously employed. The validation of the facility should be carried in accordance with GMP regulations and the data which is generated during the validation has to be maintained and reviewed further. In certain situations, where production scale has not been developed for a particular product, the validation data should be generated from pilot scale to produce the information in dossier. In such cases the pilot batch sizes are specified in this draft are as follows: i. Pilot scale batch size should be at least 10% of the production scale. e.g.: in case of solid oral dosages, if the production scale batch size is predicted as 1,000,000 the pilot scale batch size should be 100,000 i.e., 1/10 th of production scale. ii. If the production batch size is less than 1,000,000 then the pilot scale batch size for that particular product is defined by experts and the value is extrapolated to 100,000 unit’s size, and this approach is justified stating the reasons. Generally validation studies on pilot scale are not preferred. In such cases the validation is conducted on the subsequent production scale. The validation procedure description should be enclosed in the dossier. The description should contain  Manufacturing method  Investigations to be performed  Acceptance criteria  Description of control strategy proposed to maintain the validation status. It is necessary to produce the validation data on production scale in the dossier for the following situations:  Production of biological / biotech products.  Productions involving non-standard methods of sterilization  Situations where extrapolation of pilot scale validation data can’t resembles or represents the situation of production scale.  Production of dedicated products. Data submission requirements i. For non-standard sterilization methods the number of batches depends on  Process complexity  Process unpredictability  Production capability of the manufacturer. The number of batches should be a minimum of 3. For other non- standard processes the validation should be generated from the at least 1-2 production scale batches, which is supported by pilot scale validation.[1] Examples on non-standard methods: i. Pharmaceutical dosage forms  Metered dose inhalations, powder inhalers  Emulsions, suspension and other liquid dispersed parenteral,  Modified release dosage forms.  Dosage forms containing the active pharmaceutical ingredient of ≤ 2%  Other specialized dosage forms such as liposomal preparations, Nano particulate preparations, micellar preparations.[2] ii. Conventional manufacturing process involving new technologies The validation of the conventional manufacturing process is necessary when it incorporates new technologies into the process, which can affect the quality of the final product. e.g.: generally the tablet manufacturing involves wet granulation method (conventional method). The incorporation of new drying International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 6 Issue 2, 2014 Academic Sciences