Laboratory Products


How gravimetric sample preparation is helping pharmaceutical manufacturers meet the demands


of consumers, regulators, and the market Mettler-Toledo


Since the groundbreaking Barr Labs case in 1993, the FDA has issued hundreds of observations concerning poor handling of out- of-specifi cation (OOS) investigations, necessitating untold hours of lab effort as well as signifi cant fi nes. Today, gravimetric sample preparation is giving pharmaceutical companies around the world a cost-effective way to avoid OOS errors, which in turn is helping them to reduce the occurrence of time-wasting investigations, enhance productivity and safety, and save costs.


From the number of warning letters issued periodically by the US Food and Drug Administration (FDA), it is apparent that OOS results are more common in pharmaceutical manufacturing than they should be. These errors not only result in time-consuming internal investigations and fi nes. Depending on an error’s extent and market visibility, it can also make a signifi cant impact on a pharmaceutical company’s reputation and profi tability, as has been seen most recently with concerns about US-based pharmaceutical giant Johnson & Johnson’s contract manufacturing partner during COVID-19 vaccine production.


When errors in pharmaceutical research or production come to light through quality control assessment or external audit, it can be diffi cult for lab managers to pinpoint the cause of the problem, let alone assure regulators it will not happen again. Pharmaceutical groups fi nd themselves consuming valuable resources conducting or supporting an analytical lab investigation. This often leads to an uncomfortable deviation report, a more expensive corrective and preventive action (CAPA), or even a full-blown root cause analysis. This is especially true of modern complex, multistep analytical processes that are relying on smaller and smaller doses of potent active pharmaceutical ingredients (APIs) for research and formulation activities.


Why do labs have such diffi cultly getting a handle on the source of OOS results? Part of the answer can be attributed to the still-common practice of manual volumetric sample preparation. Workfl ows using volumetric fl asks have not changed signifi cantly in nearly 100 years. During this same time, however, the substances being handled have become more refi ned, more potent, and in most cases more hazardous to handle. Meeting this heightened risk safely has sometimes caused handling time to increase, even as competition has necessitated faster processing. This has sometimes had the unfortunate consequence of pitting analytical accuracy, operator safety and processing speed against each other. Previous-generation balances also played a role, as minimum weights typically did not allow direct preparation of required concentrations, with serial volumetric dilutions compounding any errors that occurred.


One solution that is helping to eliminate OOS errors - or, at the very least, ensure that sample and standard preparation is not the cause of errors that are identifi ed by regulators - is gravimetric sample preparation. The systematic change represented by this next-level dosing and weighing technology is so signifi cant that accurate processing of even the most minute quantities is making it possible to achieve precise concentrations while enhancing productivity, limiting solvent usage, and eliminating operator contact with APIs and other potentially hazardous substances altogether.


In short, gravimetric sample preparation is helping labs achieve accuracy in sample preparation workfl ows that far outpace even the most consistent human operator using volumetric methods with its inherent and well-documented variability. The addition of safety, speed, and cost-effectiveness makes the advantages of gravimetric sample preparation diffi cult to overstate.


Make multi-component standard preparation easy


A good example of the impressive gains in speed, safety and savings represented by gravimetric processes can be found when using automated powder and liquid dosing in the common lab workfl ow of preparing multi-component standards.


When manually weighing substances into a volumetric fl ask during standards creation, the risk of overshoot for each individual component is high, as is the potential cost of any errors. To reduce this risk, an operator will typically weigh a substance onto weighing paper and then transfer it into a fl ask, rather than weigh it into the fl ask directly. Does the operator then backweigh the paper to ensure no substance is left behind? If not, doubt is created about process accuracy. If so, extra time is added to the workfl ow. Neither choice is ideal.


Gravimetric preparation helps to eliminate uncertainty and save time. Both solids and solvents are measured by weight, not volume.


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124  |  Page 125  |  Page 126  |  Page 127  |  Page 128  |  Page 129  |  Page 130  |  Page 131  |  Page 132  |  Page 133  |  Page 134  |  Page 135  |  Page 136  |  Page 137  |  Page 138  |  Page 139  |  Page 140  |  Page 141  |  Page 142  |  Page 143  |  Page 144  |  Page 145  |  Page 146  |  Page 147  |  Page 148  |  Page 149  |  Page 150  |  Page 151  |  Page 152  |  Page 153  |  Page 154  |  Page 155  |  Page 156  |  Page 157  |  Page 158  |  Page 159  |  Page 160  |  Page 161  |  Page 162  |  Page 163  |  Page 164  |  Page 165  |  Page 166  |  Page 167  |  Page 168  |  Page 169  |  Page 170  |  Page 171  |  Page 172  |  Page 173  |  Page 174  |  Page 175  |  Page 176  |  Page 177  |  Page 178  |  Page 179  |  Page 180  |  Page 181  |  Page 182  |  Page 183  |  Page 184  |  Page 185  |  Page 186  |  Page 187  |  Page 188  |  Page 189  |  Page 190  |  Page 191  |  Page 192  |  Page 193  |  Page 194  |  Page 195  |  Page 196