1. Scope This SOP covers requirements for PHARMCO-AAPER s Quality Management System

of 8 1. Scope This SOP covers requirements for PHARMCO-AAPER s Quality Management System 2. Application This Standard Operating Procedure applied to the entire Quality Management System as it relevant to the operations of PHARMCO-AAPER 3. Assign Responsibility Senior Management of the company and the ISO Committee have responsibility to ensure that company operations comply with the requirements of the Quality Management System. 4. Terms and Definitions 4.1. Quality: Degree to which a set of inherent characteristics fulfills requirements 4.2. Requirement: Need or expectation that is stated, generally implied or obligatory 4.3. Management System: System to establish policy and objectives and to achieve those objectives 4.4. Quality Management System: Management system to direct and control an organization with regard to quality. The policies, procedures, practice and people that make the quality program and control the quality of our process at PHARMCO-AAPER 4.5. Quality Policy: Overall intentions and directions of an organization related to quality as formally expressed by senior management 5. Text 5.1 The Quality Management System is comprised of the following seven areas: 5.5.1. Quality Policy 5.5.2. Quality Objectives 5.5.3. Quality System Procedures (SOPs) 5.5.4. All other specific instructions and documents related to quality (ex. Work instructions, test methods, CofAs, labels etc.)

of 8 5.5.5. Results 5.5.6. Measurement and analysis of results 5.5.7. Review of results, analysis and the quality management system 5.2 General Requirements 5.5.1. In accordance with the general requirements of ISO9001 PHARMCO- AAPER has established, documented, and implemented a quality management system. This system provides for continual improvement of our effectiveness and customer focus in order to maintain customer satisfaction with our products and services in accordance with this standard 5.5.2. PHARMCO-AAPER embraces the eight quality management principles endorsed by the ISO9001:2008 standard: 5.5.1.1. Customer Focus 5.5.1.2. Leadership 5.5.1.3. Involvement of people 5.5.1.4. Process approach 5.5.1.5. System approach to management 5.5.1.6. Continual Improvement 5.5.1.7. Factual approach to decision making 5.5.1.8. Mutually beneficial supplier relationships. 5.5.3. These eight quality management principles form the basis for the quality management system standards adopted by PHARMCO-AAPER 5.5.4. PHARMCO-AAPER employs a quality management system approach that encourages organization to analyze customer requirements, define the processes that contribute to the achievement of a product that is acceptable to the customer, and keep these processes under control. Our quality management system provides the framework for continual improvement to increase the probability of enhancing customer satisfaction. It provides confidence to our organization and our customers that we are able to provide products that consistently fulfill requirement 5.5.5. At PHARMCO-AAPER, we distinguish between requirements for quality management systems that control our organization and requirements for the products we manufacture.

of 8 5.5.6. Our Quality management system consists of several features including the following: 5.5.1.1. Determining the needs and expectations of customers; 5.5.1.2. Maintaining our quality policy while creating new quality objectives for our organization based upon the fluid needs of our customers and markets 5.5.1.3. Determining the processes and responsibilities necessary to attain the quality objectives 5.5.1.4. Determining & providing the resources necessary to attain quality objectives 5.5.1.5. Establishing methods to measure effectiveness and efficiency of each process 5.5.1.6. Applying these measures to determine the effectiveness and efficiency of each process; 5.5.1.7. Determining means of preventing non-conformities and eliminating cause 5.5.1.8. Establishing and applying a process for continual improvement of the quality management system. 5.5.7. PHARMCO-AAPER has also elected to manage our organization using the process approach. This is the systematic identification and management of the processes employed within an organization and particularly the interactions between such processes. PHARMCO-AAPER has applied this concept to our own Quality Management System. An overview of this application is found below. 5.5.8. See Form G003 for Quality Management System lines of communication 5.2.8 1. Each department indicated in the Product Realization box, has a representative that serves as a coordinator for that department to the ISO Committee. 5.3 Criteria and Methods to ensure effectiveness of operation and control of processes. 5.3.1 The criteria needed for each operation will be specified in SOPs for each vital function and task. These SOPs are maintained on the K drive. These Methods used to ensure effectiveness will be training, verification of training, daily auditing tasks, formal internal audits, quality control testing of raw material and finished products and quality assurance of products and processes and external audits.

of 8 5.3.2 THE FOLLOWING IS A LIST OF SOPs IN USE 4-1-0 4-2-2 Quality Manual 4-2-3-A Master List of Controlled Documents 4-2-3-C Document and Data Control 4-2-3-D Label Creation and Control 4-2-3-E Export Labels and QC Documents 4-2-3-F Safety Data Sheets Generation & Training 4-2-3-G SOP Creation and Outline 4-2-3-H Export Documentation 4-2-4-A Control of Records 5-4-2 & 7-1-0 Quality Planning 5-6-0 Management Responsibility and Review 6-2-1-A Human Resources 6-2-2-A Hazardous Communication Program 6-2-2-B Ethanol & High Purity Solvent General Training Guide 6-2-2-C Chemical Hygiene Plan 6-2-2-D Personal Protective Equipment Program 6-2-2-E Emergency Action Plan 6-2-2-F Forklift Training Program 6-2-2-G Confined Space Program 6-2-2-H Lockout-Tag-out Program 6-2-2-I OSHA Formaldehyde Rule 6-2-2-J Training Effectiveness and Verification 6-3-0-A Infrastructure 6-3-0-B Preventive Maintenance of Production & QC Equipment 7-2-0 & 7-2-2 New Account Set Up & Customer Account Changes 7-2-1 & 7-2-2 Order Review 7-2-2-B Change to Customer Account Information 7-2-3-A Handling Customer Complaints 7-2-3-B Generation of Customer Price Schedules 7-2-3-C Customer Notification Change Process Control 7-2-4 Accounting and Customer Related Services 7-4-1 7-4-2-A Purchase Orders, Process and Information 7-4-1-B Qualifying New and Existing Vendors 7-4-2-B Purchase Orders Capital & Routine Items 7-4-3-A Testing of Incoming Chemicals 7-4-3-B Testing of Incoming Denaturant Raw Materials 7-4-3-C Receiving 7-5-0 Pest Control Program 7-5-1-A Product Files 7-5-1-C General Manufacturing Procedure 7-5-1-D Shipping from External Warehouses 7-5-1-E & 8-2-4-A Sample Collection

of 8 7-5-1-F Organic Alcohol Processing 7-5-1-G GMP Procedures for Excipients 7-5-1-H Measurement of Volume in Tanks 7-5-1-I Change Process Control 7-5-2-A Validation of Product and Processes and VMP 7-5-2-B Validation of Fill Levels 7-5-3-A Lot, Batch & Serial Numbering System 7-5-3-B Retain Sample Program 7-5-3-C & 4-2-3-I Certificates of Analysis 7-5-4 Customer Supplied Product 7-5-5-A Storage, Distribution and Drainage Systems 7-5-5-B Packaging and Shipping 7-5-5-C Inventory Control 7-6-0-A Calibration-Standardization of Measuring Equipment 8-1-0-A General Laboratory Procedure 8-2-1-A Customer Satisfaction 8-2-2-A Internal Auditing 8-2-3-A Expiration Dates Reagent Chemicals 8-2-3-B Statistical Techniques & Metrics 8-2-3-C Hazardous Waste Policy Including Lab Reagents 8-2-4-A In Process & Final Inspection and Testing 8-3-0-A Control of Non-Conforming Product 8-3-0-B Product Recall 8-5-2-A & 8-5-3 Corrective and Preventive Actions 8-5-2-B Corrective Action-Vendor Complaints 5.3.1 1. A list of SOPs is also found in the Quality Manual as well as on Form QA 512. 5.3.1 2. In addition to this, there are work instructions for each department (production, document control, customer service, accounting, and quality control departments). Quality control also has test methods. 5.3.1 3. Controlled forms are also used in carrying out the SOPs. 5.3.1 4. A complete list of categories of controlled documents and where they can be found on our internal network is located in SOP 4-2-3-A Master List of Controlled Documents. 5.4. Ensure the availability of resources and information necessary to support the operation and monitoring of these processes. This will be the responsibility of the ISO Committee and Senior Management. Refer to SOP 5-6-0 Management Responsibility and Review for more detailed information. 5.5. Responsibilities to monitor, measure and analyze processes:

of 8 5.5.1. The following are the established areas of measurement: 5.5.1.1. Financial performance 5.5.1.2. Purchasing performance 5.5.1.3. Sales Performance 5.5.1.4. Plant Performance, which includes all other areas of the company: 5.5.1.4.1. Accounting 5.5.1.4.2. Customer Service 5.5.1.4.3. Production, Shipping and Receiving 5.5.1.4.4. Quality Control, Document Control and Technical Support 5.5.1.4.5. Quality Assurance and ISO 5.5.1.4.6. Regulatory Compliance 5.5.2. Following departments and functions bear responsibilities to monitor, measure, and analyze the process: 5.5.2.1. Quality Control Product quality at various points of the quality process, vendor performance as it pertains to the quality of the raw materials, customer satisfaction as it pertains to the quality of the finished products, support of sales efforts and customer requirements for product samples and technical documentation 5.5.2.2. Sales Department Customer Satisfaction Process 5.5.2.3. Purchasing Vendor Performance, vendor reliability, and on-time delivery 5.5.2.4. Administration/Accounting Financial Performance 5.5.2.5. Production - Plant performance, including on-time shipments, line item shipped, customer satisfaction as it pertains to the quality of manufactured products and product returns 5.5.2.6. ISO/Regulatory/Safety Training Effectiveness, Regulatory Compliance. 5.5.2.7. ISO Committee Analyze Department metrics and report results to Senior Management. It is the responsibility of the ISO Committee to ensure that all goals and tasks set by the Senior Management are implemented and attained. 5.5.3. Refer to SOP 8-2-3-B Statistical Techniques and Metrics for the specific processes to be monitored in 9 different areas. 5.6. Implement actions necessary to achieve planned results and continual improvements of these processes.

of 8 5.6.1. It is the responsibility of Sr. Management to receive this analysis and recommendations for review and action. It is the responsibility of the Senior Management to set all quality goals and to ensure the necessary resources are available to achieve these goals. This review will be done during the Sr. Management Review meetings 5.7. Documentation Requirements. 5.7.1. In accordance with the ISO standard our documentation shall include the following: 5.7.1.1 Documented statement of our quality policy and quality objectives. This is found in our Quality Manual. 5.7.1.2 A Quality Manual (see SOP 4-2-2). 5.7.1.3 Documented procedures required by the ISO 9001:2008 standard. See Form QA 512 for list of SOPs. 5.7.1.4 Documented procedures needed by PHARMCO-AAPER to ensure the effective planning, operation, and control of its processes. These will also be found in SOPs and Work Instructions. 5.7.1.5 Records required by this standard. These will be kept on file by ISO Coordinator, Quality Assurance Department, and on the K-Drive in our computer system. These files are properly maintained and backed up each night on the computer system. This is an automatic system. Paper records are archived and stored in accordance with SOP 4-2-4-A Control of Records. 5. Normative References 6.1. SOP 4-2-2: Quality Manual. 6.2. SOP 4-2-3-A: Master List of Controlled Documents 6.3. SOP 4-2-3-C Document and Data Control 6.4. SOP 4-2-4-A Control of Records 6.5. SOP 5-6-0 Management Responsibility and Review 6.6. SOP 8-2-3-B Statistical Techniques and Metrics

of 8 Revision History Revision Revised Revision Date # by Reason for Revision 1.0 11/13/01 PD Original Issue created to conform to Q9001:2000 standard 2.2 02/04/08 JD Revised in accordance with the requirements of Q9001:2000 due to merger of Pharmco and AAPER quality departments. Started Revision History. 2.3 09/20/10 RG Revised in accordance with new Q9001:2008 edition. Retraining is not required for this revision. 2.4 02/24/14 EF Reviewed for accuracy against current procedures. No training required. See NCR 13-10. 2.5 05/14 AM Revised to remove SOP 7-5-1-B, Quality Plans from the In Use List under Section 5.3.2. No training required. 2.6 09/15 JMP Combined SOP 7-2-0-A, New Accounts Set Up with SOP 7-2-2-B, Change to Customers Account Information. Revised references in section 5.3.2 to new SOP Title. 7-2-0 & 7-2-2, New Account Set up & Customer Account Changes. No training required.