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  1. Guidance, Compliance, & Regulatory Information

FDA Responses to Action Items From March 18-19, 2015 Inter-governmental Working Meeting

FDA Responses to Action Items From March 18-19, 2015 Inter-governmental Working Meeting

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1.  FDA will consider the issues that states described as possible impediments to signing an MOU and aspects of the draft MOU that were identified as needing further clarification. States will also submit these issues as comments to the open docket.

 
FDA is considering the issues raised during the intergovernmental working meeting as well as the comments submitted to the docket and will make appropriate changes, as needed, in the final MOU. 
 
2.  FDA will clarify which state agencies or officials would need to sign the MOU, when finalized, if the state decides to sign it, and welcomes state input.
 
FDA is considering the issue of how state signature of the MOU should be handled and will consult with the National Association of Attorneys General to better understand who in the states can bind the state to such an agreement. 
 
3.  NABP will explore the possibility of conducting a survey of state laws and regulations pertaining to compounding to determine how the states are regulating outsourcing facilities and identifying areas of inconsistency that may pose problems. FDA will continue to discuss with the states and NABP ways they could address inconsistencies, including the possibility of a model law that states can review when establishing new laws or regulations to address outsourcing facilities to help promote more uniform outsourcing facility licensure and related requirements.
 
NABP has conducted the survey of state laws and regulations regarding outsourcing facility licensure and related requirements, and FDA has reviewed the survey to identify the areas of inconsistency among the states that might cause concern.  Some of these inconsistencies include:
  • Some states plan to inspect outsourcing facilities against USP <797> although outsourcing facilities registered with FDA under section 503B are required to comply with FDA’s current good manufacturing practice (CGMP) requirements. Most states are accustomed to inspecting against USP <797> standards, but this could cause confusion and issues for the facilities and the public.
  • States are licensing outsourcing facilities in different ways, although most states (60%) have either created a category of outsourcing facility or have under consideration legislation to create such a category. 
    • Some states are licensing them under the category “wholesalers”. This can cause confusion because one of the conditions under section 503B is a prohibition on wholesaling:  

      ``(8) Prohibition on wholesaling.--The drug will not be sold or transferred by an entity other than the outsourcing facility that compounded such drug. This paragraph does not prohibit administration of a drug in a health care setting or dispensing a drug pursuant to a prescription executed in accordance with section 503(b)(1).”

      In addition, the labeling for products compounded by an outsourcing facility must include: 

      ``(IX) the statement `Not for resale', and, if the drug is dispensed or distributed other than pursuant to a prescription for an individual identified patient, the statement `Office Use Only'”.

    • Ten states indicated they require an outsourcing facility to have a pharmacy license if they are dispensing pursuant to patient specific prescriptions; 8 states indicated they require a pharmacy license but do not specify whether this is in all cases or only if the outsourcing facility is also dispensing pursuant to prescriptions; 10 states indicate that they do not require pharmacy licenses for outsourcing facilities. We had heard but were unable to confirm through the survey that some states will not provide a pharmacy license to an outsourcing facility. 
       
    • One state requires an outsourcing facility to dispense only pursuant to patient-specific prescriptions, which is inconsistent with the business model of most outsourcing facilities. 
    • Five states said that they do not license outsourcing facilities, but did not further explain their answer.
  • FDA will continue to discuss with the states and NABP ways to resolve these inconsistencies.
 
4.  FDA will clarify the differences between USP Chapter <797> and the CGMP requirements that are applicable to outsourcing facilities. 
 
FDA is currently working on revising the draft guidance, Current Good Manufacturing Practice-Interim Guidance for Human Drug Compounding Outsourcing Facilities Under the Federal Food, Drug and Cosmetic Act in response to comments submitted during the comment period. Because FDA has not yet issued a final guidance, we are unable to provide a comparison with regard to CGMP requirements specifically applicable to outsourcing facilities at this time. 
 
5.  FDA will determine whether a modified Information Sharing Agreement could be developed for use in a state with sunshine laws, and what kinds of information could be shared under such an agreement.
 
FDA has offered the Single-Signature 20.88 Long-Term Drug Compounding Information Sharing Agreement to the states to sign. FDA will work with states that choose not to sign it to identify whether state laws are the impediment and if so, whether the agreement can be modified to allow for some types of information to be disclosed consistent with both Federal and state law. 
 
6.  FDA will determine whether the Single-Signature 20.88 Long-Term Drug Compounding Information Sharing Agreement can be signed by multiple state agencies (for example, both a state Board of Pharmacy and the state attorney general’s office).
 
FDA has determined that the Single-Signature 20.88 Long-Term Drug Compounding Information Sharing Agreement can be signed by multiple state agencies.   FDA will work with individual state agencies that wish to sign such an agreement to make the necessary modifications.
 
7. FDA will clarify when a state can use information a commissioned and credentialed state inspector obtained during a joint FDA/state inspection for a state regulatory action.
 
If a state employee is commissioned by FDA, has their own independent state authority to conduct inspections, and conducts a joint inspection with FDA, the information obtained by the state employee on their own during the inspection belongs to the state, and the state can use the information as state law permits.   If information is obtained during the inspection by the FDA investigators independent from the state inspectors, then the information could be provided to the state inspector under the commissioning agreement, but generally could not be further used to support a state action as long as it continues to be confidential information. Therefore, it would be best for the state inspector to obtain under their own authority whatever information they would need to bring a state regulatory action. 
 
8. FDA will explore when it can share information with the states from FDA’s evaluations of corrective actions that compounders implemented after an inspection or regulatory action, and what can be shared.
           
After conducting an inspection, if a Form FDA-483 is issued, FDA will send a copy of the Form FDA-483 to all 50 states with nonpublic information redacted.  Similarly, if a Warning Letter is issued, FDA will send a redacted copy of the Warning Letter to all 50 states. State officials that are commissioned by FDA pursuant to 21 U.S.C. § 372(a) may contact FDA to request an unredacted version of the Form FDA-483 or the warning letter. States that are operating under a 20.88 agreement can contact FDA to request a version of the Form FDA 483 or Warning Letter that has been redacted in accordance with the terms of the 20.88 agreement, and therefore, may contain more information than the public version. For example, it may include confidential commercial information or personal privacy information that would not normally be disclosed to the public, but not trade secrets.
 
9. FDA will explore what types of information it can share with states that do not enter into an information sharing agreement when there is a report of a serious adverse event or product quality issue and the timeframes in which it can generally share such information.
 
With respect to adverse event reports for human drugs, what can be provided depends on the content of the specific report and who reports the event, among other things. FDA intends to further clarify what can be provided as soon as possible.
 
 
10.  FDA will explore how quickly after an inspection it can share information about an outsourcing facility with the states so they can consider the information when licensing the facility.
 
After completing an inspection, if FDA issues a Form FDA-483, the firm is asked to respond to the observations within 15 days indicating whether it has an objection regarding an observation, or has implemented or plans to implement corrective actions to address the observations. Firms usually but not always submit a response. FDA reviews the observations made by the investigator, as well as the firm’s response, and considers whether regulatory action against the facility is warranted. That process may take several months to complete. In the interim, FDA encourages commissioned officials to contact FDA to discuss the findings of the inspection, corrective actions proposed by the firm, the status of the case, and any regulatory actions being contemplated. States operating under a signed 20.88 agreement could also contact FDA at Infoshare-ORA@fda.hhs.gov for information about the inspection, and FDA will share information as provided in the agreement.
 
When a state has entered into an information sharing agreement and does not have a commissioned official, FDA can only share information that is otherwise available to the public under FOIA. Such states may, however, contact the firm directly to request a copy of its correspondence with the Agency, including its response to the FDA Form-483 if one is submitted, and other related correspondence such as corrective action updates or responses to Warning Letters if one was issued.