ICH Q3D Metal Impurities & USP Elemental Impurities

Information Exchange Request

If your company has already developed information related to this topic and you have an information sheet or other document which can answer these questions adequately, please forward that document instead of filling out this form. Your own document is preferredto filling out this form unless you do not have a previously prepared document available. We are interested in obtaining information on metal impurities in the most expeditious way for both parties. The format of the document is not important providing the key information is covered.

Product Names or Codes Supplied to [COMPANY NAME]:

Please list all products purchased from the supplier in this section. Only one form should be sent to the supplier. If the answers are different for different products produced from that supplier, the supplier can attach a list of the products covered by each form or just fill out one form that would cover an entire manufacturing site if that is appropriate based on the material they produce.

Supplier Name:

Supplier Address:

Supplier Phone Number:

Supplier Email Address:

Date Form Filled Out:

Please answer the following questions and provide descriptive information where necessary to explain how your answer may apply to your products.

  1. Use in Pharmaceuticals:
  1. Do you market these products for use as a component in pharmaceuticals?
  2. If not, what market are the products intended for and do you have any metal impurity information on your products?
  3. Would you supply any metal impurity information that you may have to us for use in our risk assessment of your products for use in drug products?
  4. If not, please GO TO SECTION G of this questionnaire and SKIP SECTIONS B to F.
  1. Awareness - ICH Q3D Metal Impurities guideline and USP Elemental Impurities General Chapters:
  1. Is your company aware of the development of the draft ICH Q3D guideline on Metal Impurities and the metals which will need to be controlled in drug products in the future?
  2. Have you seen the current draft of the guideline which was reviewed by various trade associations?
  3. Is your company aware of the development of the USP Elemental Impurity General Chapters <232> and <233> and the metals and test methods which are covered?
  1. Understanding of Metal Impurity Content in your Products
  1. Have you evaluated the potential sources for metal impurities in your products?
  2. Has this evaluation included all of the metals listed in ICH Q3D and USP <232>?
  3. If not, what metals have been evaluated?
  4. Do you know if any of your products currently contain any of the listed metal impurities at levels exceeding the component concentration limits listed in ICH Q3D or USP <232>? See the references listed below for the lists of metals and limits:
    PRELIMINARY DRAFT Q3D (v6.0)REFERENCE INFORMATION

USP GENERAL CHAPTER <232>


For additional information regarding USP’s plans for implementing the Elemental Impurity requirements, see the following link:

  1. Metal Impurity Testing
  1. Have you conducted any individual metal impurity testing on your products?
  2. Do you have in-house testing capabilities or do you use outside laboratories?
  3. If you do in-house testing, what type of analytical equipment do you have that can be used to obtain the appropriate detection limits needed for the Q3D metals?
  4. Is this testing done on a routine basis or periodically?
  5. Are there any special sample preparations and/or test methodology requirements needed for testing metal impurities on your products?
  1. Expected Variability
  1. Are you aware of any significant variability that may include source, geographical location, or seasonal issues related to the level of expected metal impurities?
  2. Can long or short-term excursions in typical levels of metal impurities occur due to the raw material sources (ie; mines, biological, etc.) or manufacturing processes?
  3. Do you have an understanding of the typical variability that may occur?
  4. Is this understanding based on significant data for specific metals or just based on periodic testing performed at an in-frequent interval?
  1. Specifications
  1. Do you have any sales specifications for any specific metals in your product(s)?
  2. If so, please describe the specification(s) and whether routinemetal testingis performed for each batch of product.
  3. Are these results provided on your CoAs?
  4. Are these specifications based on compendia standards contained in specific monographs?
  5. Are the specifications based on other non-compendial standards that may be needed for other industries?
  1. Action Plans
  1. If you do not already have metal impurity data on your products, does your company plan to investigate the metal impurity levels in your products?
  2. If you do not plan to investigate the metal impurity levels, how do you plan to support your customer’s need for this information?
  3. What are the metals that you are investigating? What is the basis for this selection of metals?
  4. What is the rationale for excluding the other metals?
  5. If you plan to test products, do you anticipate any issues in achieving limits of detection based on the limits proposed for the drug products?
  6. Describe your plans for obtaining metal impurity information on your products and informing your customers of the typical levels that may be expected. Include any information you may have on existing specifications for any metals.
  7. Will these new requirements for our drug products that your product is used in impact your willingness to continue to supply your products to our company?
  1. Customer Assistance
  1. Would your company be willing to discuss specific requirements needed by our company for drug product compliance to ICH Q3D and USP <232> requirements?
  2. Please provide a contact person for further discussion on Metal Impurity requirements.
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  1. Other Information – please provide any other information or attachments you think may be useful to help us understand the potential for metal impurities in your products.