FDA’s SUPAC (Scale-Up and Post-Approval Changes) guidelines

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The FDA’s (United States Food and Drug Administration) SUPAC (Scale-Up and Post-Approval Changes) guidelines are a set of regulations that outline the procedures and requirements for making changes to a drug product after it has been approved by the FDA. These guidelines are intended to ensure that any changes made to a drug product do not negatively impact the safety, efficacy, or quality of the product.

It is important for pharmaceutical companies to comply with the SUPAC guidelines to ensure that the drugs they produce are safe and effective for patients. Failure to comply with these guidelines can result in significant fines, penalties, and legal action by the FDA.

The FDA’s SUPAC (Scale-Up and Post-Approval Changes) guidelines are divided into three levels:

  1. Level 1 changes: These are minor changes that have minimal potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 1 changes include changes to the packaging or labeling, and minor changes to the manufacturing process. These changes can typically be made through an Abbreviated New Drug Application (ANDA) or a Supplement to an ANDA.
  2. Level 2 changes: These are moderate changes that have a moderate potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 2 changes include changes to the manufacturing process, formulation, and equipment. These changes typically require a Supplement to an NDA (New Drug Application) or ANDA.
  3. Level 3 changes: These are major changes that have a significant potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 3 changes include changes to the active ingredient, the dosage form, and the route of administration. These changes typically require a full NDA or Supplement to an NDA.

The FDA also specifies the types of information that must be submitted to the FDA when making changes to a drug product. This includes information on the proposed changes, the rationale for the changes, and any data or studies that support the safety, efficacy, and quality of the drug product after the changes have been made.

Level 1 changes under the FDA’s SUPAC guidelines

Level 1 changes under the FDA’s SUPAC guidelines are considered to be minor changes that have minimal potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 1 changes include:

  • Changes to the packaging or labeling: This could include changes to the size or shape of the package, changes to the font or layout of the labeling, or the addition of new information to the labeling.
  • Minor changes to the manufacturing process: This could include changes to the equipment used in the manufacturing process, or changes to the cleaning or sanitation procedures.
  • Changes to the storage or stability conditions: This could include changes to the recommended storage temperature or humidity, or changes to the shelf life of the product.
  • Changes to the inactive ingredients: This could include the addition or removal of an inactive ingredient, or changes to the quantity of an inactive ingredient.

Level 1 changes can typically be made through an Abbreviated New Drug Application (ANDA) or a Supplement to an ANDA. These submissions are generally less extensive than those required for Level 2 or Level 3 changes, and the FDA may not require additional testing or clinical trials. However, the FDA still reviews these submissions to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product.

It’s important to note that even though Level 1 changes are considered minor, they still need to be compliant with FDA regulations and the manufacturers need to submit an ANDA or Supplement to an ANDA to the FDA for review and approval before implementing these changes.

An example of a Level 1 change under the FDA’s SUPAC guidelines

An example of a Level 1 change under the FDA’s SUPAC guidelines would be a change to the packaging of a drug product. Let’s say a pharmaceutical company has developed a medication for high blood pressure and has been selling it in a bottle with a child-resistant cap. The company may want to change the packaging to a blister pack with a push-through cap, to make it more convenient for elderly patients to open. This change would be considered a Level 1 change because it is a minor change that has minimal potential to impact the safety, efficacy, or quality of the drug product.

To implement this change, the pharmaceutical company would need to submit a Supplement to an Abbreviated New Drug Application (ANDA) to the FDA. This submission would include information on the proposed change, the rationale for the change, and any data or studies that support the safety, efficacy, and quality of the drug product after the change has been made. The FDA would then review the submission to ensure that the change does not negatively impact the safety, efficacy, or quality of the drug product.

It’s important to note that even though this change is considered minor, the FDA still review the submission to ensure the safety and efficacy of the drug product. The company also needs to make sure that this change is compliant with FDA regulations and the new packaging should be approved by the FDA before it can be marketed.

In summary, Level 1 changes under the FDA’s SUPAC guidelines are minor changes that have minimal potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 1 changes include changes to the packaging or labeling, minor changes to the manufacturing process, changes to the storage or stability conditions, and changes to the inactive ingredients. These changes can typically be made through an Abbreviated New Drug Application (ANDA) or a Supplement to an ANDA, but still need to be compliant with FDA regulations and need to be submitted for review and approval.

Level 2 changes under the FDA’s SUPAC guidelines

Level 2 changes under the FDA’s SUPAC guidelines are considered to be moderate changes that have a moderate potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 2 changes include:

  • Changes to the manufacturing process: This could include changes to the equipment used in the manufacturing process, changes to the manufacturing location, or changes to the manufacturing procedures.
  • Changes to the formulation: This could include changes to the active ingredient, changes to the inactive ingredients, or changes to the dosage form.
  • Changes to the manufacturing scale: This could include changes to the batch size or the number of batches produced per year.
  • Changes to the analytical methods: This could include changes to the methods used to test the drug product for purity, potency, or impurities.

Level 2 changes typically require a Supplement to an NDA (New Drug Application) or ANDA. The FDA may also require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product.

For example, let’s say a pharmaceutical company has developed a medication for diabetes and has been selling it in tablet form. The company may want to change the dosage form from a tablet to a capsule, to make it easier for patients to swallow. This change would be considered a Level 2 change because it is a moderate change that has a moderate potential to impact the safety, efficacy, or quality of the drug product.

To implement this change, the pharmaceutical company would need to submit a Supplement to a New Drug Application (NDA) to the FDA. This submission would include information on the proposed change, the rationale for the change, and any data or studies that support the safety, efficacy, and quality of the drug product after the change has been made. The FDA would then review the submission and may also require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product.

In summary, Level 2 changes under the FDA’s SUPAC guidelines are moderate changes that have a moderate potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 2 changes include changes to the manufacturing process, changes to the formulation, changes to the manufacturing scale, and changes to the analytical methods. These changes typically require a Supplement to an NDA (New Drug Application) or ANDA, and the FDA may also require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product.

An example of a Level 2 change under the FDA’s SUPAC guidelines

An example of a Level 2 change under the FDA’s SUPAC guidelines would be a change to the manufacturing process of a drug product. Let’s say a pharmaceutical company has developed a medication for treating heart disease and has been manufacturing it using a certain type of equipment. The company may want to change the equipment used in the manufacturing process to a newer, more efficient type of equipment. This change would be considered a Level 2 change because it is a moderate change that has a moderate potential to impact the safety, efficacy, or quality of the drug product.

To implement this change, the pharmaceutical company would need to submit a Supplement to a New Drug Application (NDA) to the FDA. This submission would include information on the proposed change, the rationale for the change, and any data or studies that support the safety, efficacy, and quality of the drug product after the change has been made. The FDA would then review the submission and may also require additional testing or clinical trials to ensure that the change does not negatively impact the safety, efficacy, or quality of the drug product. The FDA may also conduct inspections of the new manufacturing facility and process to ensure that it is compliant with FDA regulations.

It’s important to note that even though this change is considered moderate, the FDA still review the submission and may also require additional testing or clinical trials to ensure that the change does not negatively impact the safety, efficacy, or quality of the drug product. The company also needs to make sure that this change is compliant with FDA regulations and the new manufacturing process should be approved by the FDA before it can be implemented.

In summary, An example of a Level 2 change under the FDA’s SUPAC guidelines would be a change to the manufacturing process of a drug product, in this case, changing the equipment used in the manufacturing process from a certain type of equipment to a newer, more efficient type of equipment, which is considered a moderate change with moderate potential to impact the safety, efficacy, or quality of the drug product. The company can make this change by submitting a Supplement to a New Drug Application (NDA) to the FDA for review and approval. Even though this change is considered moderate, the FDA still review the submission and may also require additional testing or clinical trials to ensure that the change does not negatively impact the safety, efficacy, or quality of the drug product, and the company need to make sure that this change is compliant with FDA regulations.

Level 3 changes under the FDA’s SUPAC

Level 3 changes under the FDA’s SUPAC (Scale-Up and Post-Approval Changes) guidelines are considered to be major changes that have a significant potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 3 changes include:

  • Changes to the active ingredient: This could include changes to the source, purity, or potency of the active ingredient.
  • Changes to the dosage form: This could include changes to the route of administration, such as switching from an oral dosage form to an injectable dosage form.
  • Changes to the indication: This could include the addition of new indications or the removal of existing indications for the drug product.
  • Changes to the dosage strength: This could include changes to the amount of active ingredient in the drug product.

Level 3 changes typically require a full New Drug Application (NDA) or a Supplement to an NDA. The FDA also conducts an extensive review of these changes and may require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product. The FDA also conduct inspections of the manufacturing facility and process to ensure that they are compliant with FDA regulations.

For example, let’s say a pharmaceutical company has developed a medication for treating cancer and has been selling it in tablet form with a certain dosage strength. The company may want to change the active ingredient in the drug product, change the dosage form from a tablet to an injectable and change the dosage strength. This change would be considered a Level 3 change because it is a major change that has a significant potential to impact the safety, efficacy, or quality of the drug product.

To implement this change, the pharmaceutical company would need to submit a full New Drug Application (NDA) to the FDA. This submission would include information on the proposed change, the rationale for the change, and any data or studies that support the safety, efficacy, and quality of the drug product after the change has been made. The FDA would then conduct an extensive review of the submission and may also require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product. The FDA also conduct inspections of the manufacturing facility and process to ensure that they are compliant with FDA regulations.

It’s important to note that even though this change is considered major, the FDA still conduct an extensive review of the submission and may also require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product. The company also needs to make sure that this change is compliant with FDA regulations and the new drug product should be approved by the FDA before it can be marketed.

In summary, Level 3 changes under the FDA’s SUPAC guidelines are major changes that have a significant potential to impact the safety, efficacy, or quality of the drug product. Examples of Level 3 changes include changes to the active ingredient, changes to the dosage form, changes to the indication and changes to the dosage strength. These changes typically require a full New Drug Application (NDA) or a Supplement to an NDA. The FDA also conducts an extensive review of these changes and may require additional testing or clinical trials to ensure that the changes do not negatively impact the safety, efficacy, or quality of the drug product. The FDA also conduct inspections of the manufacturing facility and process to ensure that they are compliant with FDA regulations

Important links for guidance

SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation

SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation

SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation

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