Regulatory Open Forum

 View Only
  • 1.  Cytotoxic Injectable Lyophilized Product Plant

    Posted 04-Mar-2019 20:49
    Dear All:
    We are in the process of building a manufacturing plant for one of our "Cytotoxic Injectable Lyophilized Product".
    I have been searching for FDA guidance for the engineering/safety requirements for such a manufacturing plant. So far I have not got such informations or article on this topic.
    I will be very thankful if anyone can direct me for these informations.

    Thanking you in anticipation,

    Tapas
    (Tapas K De, Ph.D.)
    RAPS member

    ------------------------------
    TAPAS DE
    CEO
    City Of Industry CA
    United States
    ------------------------------


  • 2.  RE: Cytotoxic Injectable Lyophilized Product Plant

    Posted 05-Mar-2019 10:05
    ​Hi, Tapas - there are a few publicly available pieces of information that I am familiar with - hope this helps!

    • CFR  Parts 210 and 211 (such as 21 CFR 211.42 Design and construction features  and 21 CFR 211.67 Equipment cleaning and maintenance – Cleaning activities to prevent contamination of a drug product)
    • ICH Q7
    • ICH Q9
    • ISPE Baseline Guide: Risk-Based Manufacture of Pharmaceutical Products is referenced in some FDA presentations, and may be helpful...
    • And - EU based, but very interesting - Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities, European Medicines Agency (EMA), EMA/CHMP/ CVMP/ SWP/169430/2012, November 2014

    5.  What are the cleaning validation requirements for potent compounds (e.g., compounds that are cytotoxic, mutagenic, or have high pharmacologic activity), and is dedicated equipment required?

     
    Separation or dedication of equipment and facilities for the manufacture of potent compounds is not specifically required by CGMP regulations. However, manufacturers should identify drugs with such risks and define the controls necessary to eliminate risk of product cross-contamination in nondedicated equipment and facilities. Such controls include proper cleaning, cleaning validation, and other contaminant controls. Firms must validate that cleaning procedures are adequate to ensure that cross-contamination does not occur. CGMP regulations establish requirements to guide development and execution of cleaning validation plans.
     
    In designing a facility, firms should carefully evaluate manufacturing processes to determine the best procedural controls and floor plan-optimizing the flow of materials, equipment, and people-to help prevent product contamination.
     
    References:
    • 21 CFR 211.42: Design and construction features
    • 21 CFR 211.67: Equipment cleaning and maintenance
     

    Date: 6/8/2015





    ------------------------------
    Catherine Anderson PhD, RAC
    Associate Director - Regulatory CMC
    Hillsborough NC
    United States
    ------------------------------