SUPAC Guidelines (Scale Up & Post Approval Changes) PDF

SUPAC GUIDELINES (SCALE UP & POST APPROVAL CHANGES) 89 SUPAC capsule SUPAC brittletheincreased represents static chargebyinterfere changes recommended with at...

SUPAC GUIDELINES (SCALE UP & POST APPROVAL CHANGES) 89 SUPAC capsule SUPAC brittletheincreased represents static chargebyinterfere changes recommended with at the US FDA thetheencapsulation time of scale up or approval of NDA / ANDA. operation. In the process of developing a new drug product, the batch sizes used in the earliest human studies are small and the size of the batches is gradually increased (Scale-up). The scale-up process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as Scale- Up and Post approval Changes, or SUPAC. 90  SUPAC capsule  The SUPACbrittle Guidelines define; increased static charge interfere with the encapsulation operation.  The level of changes – Minor, Moderate and Major Changes. The level of changes may impact on formulation and quality performance in following levels; Level 1 (minor): unlikely to have detectable impact. Level 2 (moderate): could have significant impact. Level 3 (major): likely to have significant impact.  Test – Application test/ compendial test, in -vitro dissolution and in -vivo testing  Filing – Annual report, Changes being affected supplement, Prior Approval Supplement. 91 SUPAC  Dissolution data:  Case A (High permeability, high solubility): Dissolution of 85% drug in 15 min, in 900 mL of 0.1N HCl.  Case B (Low permeability, high solubility): Multi point dissolution profile in application or compendial medium at 15, 30, 45, 60, 120 minutes.  Case C (High permeability, low solubility): Multi point dissolution profile, should be performed in water, 0.1N HCl, USP buffer media pH 4.5, 6.5, 7.5 (total 5 separate dissolution profiles) at 15, 30, 45, 60, 120 minutes until either 90% of the drug from drug product is dissolved. 92 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. A. The components or composition, B. The site of manufacture, C. The batch size, D. The manufacturing (process and equipment). 93 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. A) The components or composition changes: This section focuses on changes in excipients in the drug product. SUPAC-MR (Modified release) - Excipient critical or non-critical to the Modified drug release. Changes in non-release and release controlling excipients. SUPAC-SS (Sustained release) - Changes in preservative in semisolid formulations. SUPAC-IR (Immediate release) - Changes for immediate-release solid oral dosage forms. 94  SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. A) The components or composition changes:  Test – Application test/ compendial test, in -vitro dissolution and in -vivo testing  Filing– Annual report, Changes being affected supplement, Prior Approval Supplement. 95 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. B) The changes in manufacturing site: Changes in location of ‣ the site of manufacture ‣ packaging operations ‣ analytical testing laboratory Do not include any scale-up changes, changes in manufacturing (including process and/or equipment), or changes in components or composition. Current Good Manufacturing Practice (cGMP) inspection. 96 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: B) The changesoperation. in manufacturing site:  Level I Changes – ‣ Site change within a single facility, ‣ where the equipment, standard operating procedures (SOP's), environmental conditions (e.g., Temperature and humidity) and controls, & personnel are common.  Test Documentation- ‣ Application/ compendia requirements in chemistry, ‣ Dissolution and in vivo Bioequivalence - None.  Filing Documentation- Annual report. 97  SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: B) The changesoperation. in manufacturing site:  Level II Changes – Site changes within a contiguous (connected) campus or between facilities in adjacent city blocks, where equipments, SOPs, environmental changes & control, personnel are common to both manufacturing sites.  Test Documentation–  Filing Documentation- Annual report ‣ Application/ compendial requirements ‣ Notification of Location of new site ‣ Updated batch records ‣ SUPAC – MR - Multi-point dissolution profiles (15,30,45,60 and 120 min) USP buffer media at pH 4.5-7.5 for extended release. different media e.g., Water, 0.1N HCl, & USP buffer media at pH 4.5 and 6.8 for delayed release until 80% of drug released. 98 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: B) The changesoperation. in manufacturing site:  Level III Changes – Site changes to a different campus, which is NOT on the same original contiguous site or where the facilities are NOT in adjacent city block. Equipments, SOPs, environmental changes & control, personnel are common to both manufacturing sites.  Test Documentation –  Filing Documentation- Annual report, prior ‣ Application/compendial requirements. approval of supplement. ‣ Notification of Location of new site. ‣ Updated batch record. ‣ SUPAC - IR: Multi-point dissolution profile in the application/compendial medium. ‣ SUPAC - MR: Multi-point dissolution profiles (15, 30, 45, 60 and 120 min) USP buffer media at pH 4.5-7.5 for extended release). Different Media e.g., Water, 0.1N HCl, and USP buffer 99 media at pH 4.5 and 6.8 for delayed release until 80 % of Drug Released. SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. C) Changes in Batch Size (Scale-Up/Scale-Down) : Post-approval changes in the size of a batch from the pivotal/pilot scale bio batch material to larger or smaller production batches call for submission of additional information in the application. Compliance with cGMP’s. All scale-up changes should be properly validated. The minimum batch size for the pivotal clinical trial batch or bio batch should be at least 100,000 dosage units/ 100 kg/ 10% of a production batch, whichever is larger. Scale-down below 100,000 dosage units is not covered by this guidance. 100 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. C) Changes in Batch Size (Scale-Up/Scale-Down) :  Level I Changes – ‣ Change in batch size up to & including a factor of 10 times the size of the pilot/biobatch.  Test Documentation – ‣ Updated batch records ‣ Application/compendial requirements ‣ Stability  Filing Documentation- Annual report (long term stability data). 101  SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. C) Changes in Batch Size (Scale-Up/Scale-Down) :  Level II Changes –  Changes in batch size beyond a factor of 10 times the size of the pilot or bio batch, No other changes.  Test Documentation – ‣ Chemistry Documentation, Application/ compendial release requirements. Notification of change and submission of updated batch records. ‣ Stability testing: One batch with three months accelerated stability data and one batch on long-term stability. ‣ Dissolution Documentation (case B) ‣ In -Vivo Bioequivalence  Filing Documentation- Changes being affected supplement; annual report (long-term stability data). 102 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. (process/equipment): D) Changes in the manufacturing I) Equipment –  Level I Changes:  Alternate equipment of the same design and principles as automated equipment.  Change from non-automated or non-mechanical equipment to automated or mechanical equipment to move ingredients.  Test Documentation – Updated batch records, Application/compendial requirements and stability.  Filing Documentation- Prior approval supplement with justification for change; annual report (long-term stability data). 103 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. (process/equipment): D) Changes in the manufacturing I) Equipment -  Level II Changes:  Change to equipment of different design and different principle.  Test Documentation – Updated batch records, Application/compendial requirements and stability. SUPAC – IR - Multi-point dissolution profiles in multiple media (case C). SUPAC – MR - Multi-point dissolution profiles in multiple media (case C).  Filing Documentation- Annual report and changes being affected Supplement. 104 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. (process/equipment): D) Changes in the manufacturing II) Process -  Level I Changes:  This category includes process changes including changes such as mixing times and operating speeds within approved application/ validation ranges.  Test Documentation – Updated batch records, Application/compendial requirements and stability.  Filing Documentation- Annual report 105 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. (process/equipment): D) Changes in the manufacturing II) Process -  Level II Changes: process changes including changes such as mixing times and operating speeds outside of application/ validation ranges.  Test Documentation – Updated batch records, Application/compendial requirements and stability. ‣ SUPAC - IR - Multi-point dissolution profile ‣ SUPAC- MR - Multi-point dissolution profiles in multiple media ‣ SUPAC – SS - In vitro release test Documentation.  Filing Documentation- Annual report and changes being affected Supplement. 106 SUPAC capsule  SUPAC brittle provide guidelines increased static charge interfere recommendations with thechanges for post-approval encapsulation in: operation. (process/equipment): D) Changes in the manufacturing II) Process -  Level III Changes:  Changes in the type of process used (e.g. wet granulation to direct compression).  Test Documentation – Updated batch records, Application/compendial requirements, stability, bio-study and IVIVC. ‣ SUPAC - IR - Multi-point dissolution profile. ‣ SUPAC- MR - Multi-point dissolution profiles in multiple media.  Filing Documentation- Prior approval supplement with justification; annual report (long- term stability data). 107  capsule brittle increased static charge interfere with the encapsulation operation. 108 Contract manufacturing capsule of Production brittle goodsincreased static by one firm, charge under interfere the label with the or brand encapsulation of another firm. operation. Contract manufacturers provide such service to several (even competing) firms based on their own or the customers' designs, formulas, and/or specifications. Also called private label manufacturing. Contract manufacturing is a process that established a working agreement between two companies. As part of the agreement, one company will custom produce parts or other materials on behalf of their client. 109 Contract manufacturing In most cases,brittle capsule the manufacturer will also increased static handleinterfere charge the ordering withand theshipment processes for encapsulation the client. operation. As a result, the client does not have to maintain manufacturing facilities, purchase raw materials, or hire labor in order to produce the finished goods. The basic working model used by contract manufacturers translates well into many different industries. There are a number of examples of pharmaceutical contract manufacturing currently functioning today, as well as similar arrangements in food manufacturing, then creation of computer components and other forms of electronic contract manufacturing. 110  Contract manufacturing capsule Even brittle industries increased like personal static care and charge interfere with hygiene products, the encapsulation automotive parts, and medical operation. supplies are often created under the terms of a contract manufacture agreement. In order to secure contract manufacturing jobs, the contract manufacturer usually initiates discussions with the potential client. The task is to convince the prospective customer that the manufacturer can use their facilities to produce quality goods that will meet or exceed the expectations of the customer. At the same time, the manufacturer will demonstrate how the overall unit cost of production to the customer will be less than any current production strategies in use, thus increasing the amount of profit that will be earned from each unit sold. 111 Contract manufacturing capsule  Scope brittle increased of contract static charge interfere with the encapsulation manufacturing operation. Mappings are only provided for A2A communication (between the OED's ERP system and SAP* SNC*) from IDoc to XML and vice versa. This business scenario does not cover the tracking of the manufacturing process (production phases) that takes place at the contract manufacturer's site - it does not take into account the current production phase at the contract manufacturer' site. Consequently, the OED planner cannot predict the supply situation of finished goods. *OED- Office of Enterprise Development * SAP- Supply Network Planning * SNC- Supply Network Collaboration 112 Contract manufacturing capsule  Scope brittle increased of contract static charge interfere with the encapsulation manufacturing operation. The scope of the Contract Manufacturing Procurement business scenario outlined in this documentation only concerns the customer side. This business scenario does not cover how an ERP (Enterprise Resource Planning) system on the supplier's side (that is, the contract manufacturer's side) receives messages sent by the customer, and how it deals with the additional information (for example, components) submitted with these messages. 113 Contract manufacturing capsule brittle increased static charge interfere with the encapsulation  Advantages operation. For the manufacturer, there is the guarantee of steady work. Having contracts in place that commit to certain levels of production for one, two and even five year periods makes it much easier to forecast the future financial stability of the company. For the client, there is no need to purchase or rent production facilities, buy equipment, purchase raw materials, or hire and train employees to produce the goods. There are also no headaches from dealing with employees who fail to report to work, equipment that breaks down, or any of the other minor details that any manufacturing company must face daily. 114 Contract manufacturing capsule brittle increased static charge interfere with the encapsulation  Advantages operation. All the client has to do is generate sales, forward orders to the manufacturer & keep accurate records of all income and expenses associated with the business venture. The general concept of contract manufacturing is not limited to the production of goods. Services such as telecommunications, Internet access, and cellular services can also be supplied by a central vendor and private branded for other customers who wish to sell those services. Doing so allows the customer to establish a buy rate from the vendor, then resell the services at a profit to their own client base. 115 Contract manufacturing capsule brittle  Limitations increased of contract static charge interfere with the encapsulation manufacturing operation. Once a schedule line in the ERP (Enterprise Resource Planning) purchase order is changed, the date and quantity data originally requested are lost. Even if the information is stored in SAP SNC, it is not possible to send this information to the CM (Contract manufacturer). No data import control functions are provided for messages sent from the CM to SAP SNC. The bill of material (BOM) is not available in SAP SNC. 116 Contract manufacturing capsule brittle  Limitations increased of contract static charge interfere with the encapsulation manufacturing operation. New purchase order items cannot be created in SAP SNC. Product substitution is not supported. Scheduling agreements for the subcontracted material are not allowed. 117 Introduction to platform technology A group of technologies that can be used as a base and upon which other technologies or processes or other applications can be built-up. Platform technologies are systems that distribute the system out into different levels of abstraction. This is done in order to differentiate between core – platform – functions, and the application layer that sits on top of, and draws upon, these underlying common services. The platform approach allows process development efforts to focus on solving problems without defining standard conditions. Introduction to platform technology  Types of platform technology: Operating systems provide the basic services required to use hardware.  Computing Platforms.  Database Platforms.  Storage Platforms.  Application Platforms.  Mobile Platforms.  Web Platforms. Introduction to platform technology Pharmaceutical Platform technologies: Pharmaceutical Platform technologies are considered a valuable tool to improve efficiency and quality in drug product development. The basic idea is that a platform, in combination with a risk-based approach, is the most systematic method to leverage prior knowledge for a given new molecule. Platform technology is becoming a popular industry approach for bioprocessing. Furthermore, such a platform enables a continuous improvement by adding data for every new molecule developed by this approach, increasing the robustness of the platform. But it has often been said that access to the latest technological platforms to aid efficient drug discovery and development is limited to Big Pharma, which can more easily justify the costs of creating and operating these platforms. Introduction to platform technology Examples of Morden Pharmaceutical Platform Technologies: ‣ Assembly Biosciences’ GemicelTM ‣ DiffCORETM [GSK]* ‣ DNA based Vaccines for Infectious Diseases by Vical [GSK]*= GlaxoSmithKline Books that you can refer… 124