SUPAC Guidelines (Scale Up Post Approval Changes) - Level of changes

 SUPAC Guidelines (Scale Up Post Approval Changes)

Scale up: 

It is the process of increasing something size, amount or production from small scale (less amount) production to large scale (large amount) production.

It is the process of increasing batch size and out volume of production.

SUPAC:

It is the scale up post approval changes (changes made after approval) like formulation of drug, size, site of manufacturing, equipment etc.

FDA and American association of pharmaceuticals scientist (AAPS) provided the scientific foundation for the scale-up and post approval changes required for immediate release of product called SUPAC.

SUPAC guidelines are extremely important in the pharmaceutical industry as drug maintain quality. After a drug has been approved numerous changes may be applied by the company which could be potentially consistency and quality of the drug.

SUPAC guidelines refers: 

1. Level of changes

• Minor changes
• Moderate changes
• Major changes

2. Test documentation

• Application or compendial test
• In vitro dissolution
• In vivo

3. Filing documentation

• Annual report
• Changes being affected supplement
• Prior approval supplement

There are some categories which include SUPAC guidelines:

1. SUPAC-IR (intermediate releases)
2. SUPAC-MR (modified release)
3. SUPAC-SS (non-sterile semi solid doges form)

Changes can be takes place in the following areas: 

(It mainly provides guidelines to the following)

• Composition and components of the drug product

• Changes in the manufacturing site.

• The product's scale up process.

• Equipment used in the manufacturing.

• Packing of the product

SUPAC is post approval which denotes the new product which has been approved via the following and finally reaches in the market...

• New drug application (NDA)

• Investigational new drug application (INDA)

• Food drug administration (FDA)

• Abbreviated new drug application (ANDA)

• Abbreviated antibiotic new drug application (AADA) 

Requirements for post approval changes:

How can we update or changes the information in an approved application?

• Composition and components.

• Site changes

• Changes in the batch size

• Changes in manufacturing

• Changes in specification

• Changes in packaging.

There are mainly 3 level of changes in SUPAC which include manufacturing, chemistry, controls test, invitro dissolution test and bioequivalence test for one of each level

1. Composition and components

• In this, the guidance is mainly focus on the excipients of the product.
• Qualitative changes of the excipients should be only those excipients which are present in approved drug products for the specific route of administration.
• The changes in excipients should not exceed the amount previously approved in products with the same specific route of administration.

Level of changes:

Level 1:

• In this, the changes are those that are unlikely to have any detectable impact on formulation, quality and performance.
• The changes occur up to 5% of approved amount.

example: Deletion or partial deletion of an ingredient intended to affect the colour, fragrance of flavor of the drug product.

Level 2:

• In this, the changes are those that that could have a significant impact on formulation, quality and performance.
• The change occurs between greater than 5% and less than or equal to 10% of approved amount of the individual product.

example: Changes in particle size distribution of the substance, if the drug is in suspension.

Level 3:

• In this, the changes are those that are likely to have a significant impact on formulation, quality and performance.
• The changes occur greater than 10% of the approved amount of the product. 

 example:

-Any qualitative and quantitative changes i an excipient beyond the ranges noted in level 2.
-The changes are in crystalline form of the drug substance, if the drug is in suspension.

2. Site changes

• Site changes include the changes in location of the site of manufacture for both company-owned and contract manufacturing facilities and do not include any scale-up changes.
• Changes in manufacturing including process and equipment.
• New manufacturing locations or site should follow current Good Manufacturing Practice (cGMP) inspection.

Level of change:

Level 1:

• In this, the changes consist of site changes within a single facility where the same equipment, standard operating procedures (SOP's), environmental conditions
• Controls the personnel common to both manufacturing sites are used, and where no changes are made to the manufacturing batch records, except for administrative information and the location of the facility.

Level 2:

• In this, changes include the site changes within a contiguous campus, or between facilities in adjacent city blocks, where the same equipment, SOP's, environmental conditions.
• Controls the personnel common to both manufacturing sites are used, and where no changes are made to the manufacturing batch records, except for administrative information and the location of the facility.  

Level 3:

• In this, the changes include in manufacturing site to a different campus.
• A different campus is defined as one that is not on the same original contiguous site or where the facilities are not in adjacent city blocks.
• The same equipment, SOP's, environmental conditions, and controls should be used in the manufacturing process at the new site, and
• No changes may be made to the manufacturing batch records except for administrative information, location and language translation, where needed. 

3. Changes in batch size:

• Post approval changes in the batch size from the pilot scale bio batch material to larger or smaller production batches call for submission of additional information in the application.
• Scale-down below 100,000 dosage units is not covered by this guidance.
• All scale-up changes should be properly validated and, where needed, inspected by appropriate agency personnel.

4. Changes in manufacturing:

• Manufacturing changes may affect both equipment used in the manufacturing process and the process itself.

Click here to download full pdf notes.

Share this page to your friends, for any need comment below